News & press releases

2016

October, 3rd
Detection and Characterization of Circulating Tumor Associated Cells in Metastatic Breast Cancer Info+

Article
Detection and Characterization of Circulating Tumor Associated Cells in Metastatic Breast Cancer
Zhaomei Mu 1,*, Naoual Benali-Furet 2, Georges Uzan 2, Anaëlle Znaty 2, Zhong Ye 3,
Carmela Paolillo 4, Chun Wang 3, Laura Austin 3, Giovanna Rossi 1, Paolo Fortina 4,5,
Hushan Yang 3 and Massimo Cristofanilli 1,*
1 Department of Medicine-Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center,
Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; giovirossi85@yahoo.it
2 ScreenCell SA, Sarcelles 95200, France; benali@screencell.com (N.B.-F.); guzan@screencell.com (G.U.);
aznaty@screencell.com (A.Z.)
3 Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University,
Philadelphia, PA 19107, USA; Zhong.Ye@jefferson.edu (Z.Y.); Chun.Wang@jefferson.edu (C.W.);
laustin@gmail.com (L.A.); hushan.yang@jefferson.edu (H.Y.)
4 Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University,
Philadelphia, PA 19107, USA; carmela.Paolillo@jefferson.edu (C.P.); paolo.Fortina@jefferson.edu (P.F.)
5 Department of Molecular Medicine, University of Rome “Sapienza”, Rome 00185, Italy
* Correspondence: zhaomei.mu@northwestern.edu (Z.M.); massimo.cristofanilli@nm.org (M.C.);
Tel.: +1-312-503-5489 (Z.M.); +1-312-503-5488 (M.C.)
Academic Editor: Dario Marchetti
Received: 5 August 2016; Accepted: 23 September 2016; Published: 30 September 2016
Abstract: The availability of blood-based diagnostic testing using a non-invasive technique holds
promise for real-time monitoring of disease progression and treatment selection. Circulating tumor
cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC).
The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant
cells and description of the relevant genetic alterations that may change according to disease
progression and therapy resistance. However, the molecular characterization of CTCs remains
a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the
enrichment, isolation and molecular characterization of CTCs. In this pilot study, we evaluated
circulating tumor associated cells in one blood draw by size exclusion technology and cytological
analysis. Among 30 prospectively enrolled MBC patients, CTCs, circulating tumor cell clusters (CTC
clusters), CTCs of epithelial–mesenchymal transition (EMT) and cancer associated macrophage-like
cells (CAMLs) were detected and analyzed. For molecular characterization of CTCs, size-exclusion
method for CTC enrichment was tested in combination with DEPArray™ technology, which allows
the recovery of single CTCs or pools of CTCs as a pure CTC sample for mutation analysis. Genomic
mutations of TP53 and ESR1 were analyzed by targeted sequencing on isolated 7 CTCs from a patient
with MBC. The results of genomic analysis showed heterozygous TP53 R248W mutation from one
single CTC and pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and
pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The results of this study
reveal that size-exclusion method can be used to enrich and identify circulating tumor associated
cells, and enriched CTCs were characterized for genetic alterations in MBC patients, respectively.
Keywords: metastatic breast cancer (MBC); circulating tumor associated cells; circulating tumor
cells (CTCs); circulating tumor cell clusters (CTC clusters); epithelial–mesenchymal transition (EMT);
cancer associated macrophage-like cells (CAMLs); size-exclusion technology

detection-and-characterization-of-circulating-tumor-associated-cells-in-metastatic-breast-cancer-2016

September, 28th
ScreenCell Establishment Licence Canada MD class 1 Info+

Establishment Licence

Medical Device


SCRENCELL

10 Avenue Charles Péguy

Centre Roger Pérez

95200 Sarcelles France


This Licence is issued in accordance with the Medical Devices Regulation of Food and Drugs Act for the following activities:

Manufacture Devices for Distribution: CLASS I

LICENCE NUMBER: 7044

canada-4 canada

                             Issue Date: 2016-06-02

May, 30th
Droplet Digital PCR of circulating tumor cells from colorectal cancer patients can predict KRAS mutations before surgery Info+

Droplet Digital PCR of circulating tumor cells from colorectal cancer patients can predict KRAS mutations before surgery.
Jérôme Alexandre Denis1,2,3, Alexia Patroni4, Erell Guillerm1,5, Dominique Pépin2, Naoual Benali-Furet6, Janine Wechsler6, Gilles Manceau1,4, Maguy Bernard2, Florence Coulet1,5; Annette K. Larsen3, Mehdi Karoui1,4, Jean-Marc Lacorte1,2, 7
1. Sorbonne Universités, UPMC Univ. Paris 06, F-75005, Paris, France.
2. Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Oncology and Endocrine Biochemistry, Paris, France.
3. Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Institut National de la Santé et de la Recherche Médicale (INSERM) U938 and Institut Universitaire de Cancérologie (IUC), Université Pierre et Marie Curie (UPMC), Sorbonne Universities, Paris, France.
4. Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Digestive and Hepato-Pancreato-Biliary Surgery, Paris, France.
5. Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of oncogenetics and molecular angiogenetics, Paris, France.
6. ScreenCell SA, Sarcelles, France
7. INSERM, UMR_S 1166, Institute of cardiometabolism and nutrition. ICAN. Paris, France

Abstract:
In colorectal cancer (CRC), KRAS mutations are a strong negative predictor for treatment with the EGFR-targeted antibodies cetuximab and panitumumab. Since it can be difficult to obtain appropriate tumor tissues for KRAS genotyping, alternative methods are required. Circulating tumor cells (CTCs) are believed to be representative of the tumor in real time. In this study, we explored the capacity of a size-based device for capturing CTCs coupled with a multiplex KRAS screening assay using droplet digital PCR (ddPCR). We showed that it is possible to detect a mutant ratio of 0.05 % and less than one KRAS mutant cell per mL total blood with ddPCR compared to about 0.5% and 50-75 cells for TaqMeltPCR and HRM. Next, CTCs were isolated from the blood of 35 patients with CRC at various stage of the disease. KRAS genotyping was successful for 86% (30/35) of samples with a KRAS codon 12/13 mutant ratio of 57% (17/30). In contrast, only one patient was identified as KRAS mutant when size-based isolation was combined with HRM or TaqMeltPCR. KRAS status was then determined for the 26 available formalin-fixed paraffin-embedded tumors using standard procedures. The concordance between the CTCs and the corresponding tumor tissues was 77% with a sensitivity of 83%. Taken together, the data presented here suggest that is feasible to detect KRAS mutations in CTCs from blood samples of CRC patients which are predictive for those found in the tumor. The minimal invasive nature of this procedure in combination with the high sensitivity of ddPCR might provide in the future an opportunity to monitor patients throughout the course of disease on multiple levels including early detection, prognosis, treatment and relapse as well as to obtain mechanistic insight with respect to tumor invasion and metastasis.

The paper has been accepted for publication in Molecular Oncology, in press.

2015

December, 10th
SABCs 2015: Detection and Characterization of CTCs Isolated by ScreenCell® Size Exclusion Technology in Metastatic Breast Cancer Info+

SABCs 2015 : Poster Session 2 – Thursday, December 10 7:30 am – 9:00 am

https://www.sabcs.org/Program/Poster-Sessions/Poster-Session-2

Background: Circulating Tumor cells (CTCs) detection has prognostic and predictive implications in patients with metastatic breast cancer (MBC). Genomic and phenotypic analysis of CTCs hold enormous promise as blood-based molecular characterization and monitoring disease progression and treatment benefit with a strong potential to be translated into more individualized targeted treatments. FDA-approved CellSearch™ detection allows only enumeration of CTCs expressing EpCAM without molecular characterization. CTCs represent very heterogeneous populations of tumorigenic cancer cells and some subpopulations have undergone epithelial-Mesenchymal transition (EMT), which is associated metastasis process and an unfavourable outcome. EpCAM-based enrichment technique has failed to detect EMT subpopulations due to the decreased expression or loss of epithelial markers. Non-EpCAM-based approaches are needed for identifying EMT CTCs. The ScreenCell® devices are single-use and low-cost innovative devices that use a filter for enrichment-free isolation of CTCs by a two-steps combining size-based separation and staining using different markers. The DEPArray™ system is the ideal downstream isolation system to collect single or pooled CTCs for molecular and genetic analysis. In this study, we evaluated the feasibility of achieving CTCs detection/enumeration using ScreenCell® filtration followed by single cell isolation with the DEPArray™ in MBC patients.

Methods: The first part of the study consisted in evaluating CTCs detection/enumeration in 30 patients with stage III and stage IV breast cancer. 3 mL of whole blood in an EDTA or Transfix tubes was collected and processed on the ScreenCell® Cyto device following the instructions of the supplier. CTCs were stained with cytokeratin (CK-8, 18, and 19), leukocyte antigen (CD45), and a nuclear dye (DAPI) and counted under fluorescence microscope. CTCs were identified as positive staining for CK and DAPI and negative staining for CD45 (CK+/DAPI+CD45-). In the second part, After enrichment, CTCs were stained with CK, CD45, and DAPI and sorted with DEPArray™ Platform (Silicon Biosystems, Inc). Single CTCs were collected and the DNA of each single CTCs was amplified with Ampli1™ WGA kit, and the genome integrity index (GII) was assessed by Ampli1™ QC kit (Silicon Biosystems, Inc). Library was constructed and whole exome sequencing (WES) of DNA mutations was conducted.

Results: Twenty patient samples had CTCs detected (66.7%), the number of CTCs was 1 to 347 per 3.0 ml of whole blood. CTC-clusters were detected in 7 patient samples (23.3%). Single CTCs were collected on DEPArray™ platform after enrichment with ScreenCell filtration. GII was confirmed with the presence of short, medium, and long DNA fragments (3 to 4 PCR bands) in the WGA library by PCR-based assay. All collected CTCs showed high GII as measured by Ampli1™ QC kit (GII ≥ 3) for WES of DNA mutations. The data analysis of WES results is under processing.

Conclusions: ScreenCell® filtration is simple and effective devices to isolate CTCs and identify CTC-clusters. Isolation of single cells for molecular analysis using the combination of ScreenCell® filtration and DEPArray™ Platform is feasible for genetic characterization of CTCs.

Authors: Zhaomei Mu1, Naoual Benali-Furet2, Georges Uzan2, Zhong Ye1, Carmela Paolillo1, Laura Austin1, Chun Wang1, Rebecca Jaslow1, Hushan Yang1, Paolo Fortina1,
Massimo Cristofanilli1

Institutions: 1Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States, 19107 and 2ScreenCell, Sarcelles, France, 95200.

SABCs-Poster P2 02 14 Massimo Cristofanilli dec 2015

November, 4th
ASI Partners with ScreenCell to Develop a Novel, Non-Invasive Prenatal Diagnosis Based on Circulating Fetal Cells Info+

November 4, 2015

ASI Partners with ScreenCell to Develop a Novel, Non-Invasive Prenatal Diagnosis Based on Circulating Fetal Cells

Partnership is intended to overcome limitations of existing methods, widening the range of genetic abnormalities that can be screened.

Carlsbad CA, US and Sarcelles, FRANCE – November 4, 2015 – Applied Spectral Imaging (ASI, www.spectral-imaging.com) and ScreenCell announced today that they have entered into a global partnership to develop a procedure enabling genetic analysis of trophoblastic fetal cells for prenatal diagnoses of genetic diseases. The partnering leverages ASI’s most advanced automated imaging platforms supporting FISH, brightfield and unique spectral image acquisition and analysis for karyotyping and FISH, and ScreenCell’s proprietary method for isolating circulating fetal cells.

Prenatal diagnosis is routine across the world and is especially valuable for women at advanced maternal age and those with high risk for chromosomal abnormalities. However, such diagnosis is often performed using invasive procedures, introducing the risk of complications for both the mother and fetus. In recent years, non-invasive prenatal testing (NIPT) on circulating cell free fetal DNA (cffDNA) in the maternal blood has been introduced, a method that combines advantages of both lower risk and cell-based specificity, but also has serious limitations.

ASI and ScreenCell are partnering to develop a new and highly reliable procedure for NIPT which would resolve these limitations. This will be achieved by successfully isolating and analyzing circulating fetal cells to enable accurate diagnosis for a much wider range of genetic abnormalities than currently available methods allow.

“Our expertise as a technology leader affords us excellent perspective on this rapidly advancing field of diagnostics. ASI is uniquely positioned to offer ScreenCell unmatched experience and imaging capabilities”, said Limor Shiposh, ASI’s Chief Executive Officer. “Adding ScreenCell’s method for non-invasive prenatal testing to our extensive imaging offering will allow us to offer our customers highly advanced Rare Cell detection and analysis, and we feel fortunate to be able to partner with ScreenCell on such an important project”, Mrs. Shiposh added.

“We see ASI as the ideal partner for advancing non-invasive prenatal diagnosis based on circulating fetal cells,” said David Znaty, Chief Executive Officer of ScreenCell. “Our goal is to develop and introduce a new, low risk and high yield testing method that combines our great success in isolating Rare Circulating Cells together with the highly intelligent imaging and analysis capabilities provided by ASI’s advanced platforms. We are very excited about developing such a comprehensive solution.”

About Applied Spectral Imaging (ASI)

Founded in 1993, ASI is a global leader in the development of imaging solutions for pathology, cytogenetic, and life science research.

ASI’s GenASIs™ automated imaging platforms for pathology and genetic analysis provide advanced diagnostic aids for pathologists and cytogeneticists, with reproducible and reliable results. The GenASIs platform can be used with most brightfield or fluorescence microscopes and supports manual and automatic scanning for a wide range of workflows and applications, to best suit the needs, size and budget of any lab.

ASI’s applications are also US FDA cleared for BandView Karyotyping, FISHView, SpotScan (for CEP XY, UroVysion, ALK and HER2/neu FISH), and HiPath (for IHC Family: HER2, ER, PR and Ki67).

 

About ScreenCell

ScreenCell was founded with the objective of designing and producing a simple but revolutionary technique allowing the fast and effective isolation of Rare Circulating Cells, yielding high-quality cellular and molecular characterization.

ScreenCell has developed a full range of downstream technologies enabling the characterization of isolated cells (expression of markers, detection of genetic mutations and aneuploidy) and is a pioneer in Circulating Tumor Cell (CTC) technologies.

ScreenCell is dedicated to creating technologies enabling molecular pathology, cell culture and enumeration, and cytomorphology evaluation, and sells a full range of point-of-care devices for in vitro diagnostics (IVD) assays and platforms.

 

 

For More Information Contact:

Mrs. Limor Shiposh, Chief Executive Officer Mr. David Znaty, Chief Executive Officer
Applied Spectral Imaging

Carlsbad California, US

Tel: +1 800-611-3466

sales@spectral-imaging.com

www.spectral-imaging.com

ScreenCell

Sarcelles, FRANCE

Tel. +33 (0)1 82 32 31 30

contact@screencell.com

www.screencell.com

 

November, 2nd
ScreenCell sponsors Molecular Med TRI-CON 2016, March 7-9 2016, San Francisco, CA Info+

March 7 – 9, 2016 | Moscone North Convention Center | San Francisco, CA
Part of the 23rd International Molecular Medicine Tri-Conference

Circulating Tumor Cells : Enabling Liquid Biopsy

Monday, March 7
1:15 Luncheon Presentation I:

Size-Based Isolation of Circulating Tumor Cells Associated to Droplet Digital PCR Allow Prediction of KRAS Mutations in Patients with Colorectal Cancer before Tumor Surgery.

Jérôme A. Denis, M.D., Ph.D., Sorbonne Universités, Paris, France

http://www.triconference.com/Circulating-Tumor-Cells/

 

April, 2nd
Circulating Tumor Cells Found in Patients With Localized and Advanced Pancreatic Cancer. Info+

Pancreas. 2015 Mar 27. [Epub ahead of print]

Circulating Tumor Cells Found in Patients With Localized and Advanced Pancreatic Cancer.

Kulemann B1, Pitman MB, Liss AS, Valsangkar N, Fernández-Del Castillo C, Lillemoe KD, Hoeppner J, Mino-Kenudson M, Warshaw AL, Thayer SP.

Abstract

OBJECTIVES:

Isolation of circulating tumor cells (CTCs) holds the promise of diagnosing and molecular profiling cancers from a blood sample. Here, we test a simple new low-cost filtration device for CTC isolation in patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS:

Peripheral blood samples drawn from healthy donors and PDAC patients were filtered using ScreenCell devices, designed to capture CTCs for cytologic and molecular analysis. Giemsa-stained specimens were evaluated by a pancreatic cytopathologist blinded to the histological diagnosis. Circulating tumor cell DNA was subjected to KRAS mutational analysis.

RESULTS:

Spiking experiments demonstrated a CTC capture efficiency as low as 2 cells/mL of blood. Circulating tumor cells were identified by either malignant cytology or presence of KRAS mutation in 73% of 11 patients (P = 0.001). Circulating tumor cells were identified in 3 of 4 patients with early (≤American Joint Committee on Cancer stage IIB) and in 5 of 7 patients with advanced (≥ American Joint Committee on Cancer stage III) PDAC. No CTCs were detected in blood from 9 health donors.

CONCLUSIONS:

Circulating tumor cells can be found in most patients with PDAC of any stage, whether localized, locally advanced, or metastatic. The ability to capture, cytologically identify, and genetically analyze CTCs suggests a possible tool for the diagnosis and characterization of genetic alterations of PDAC.

 

March, 6th
BREAKTHROUGH IN DIAGNOSIS OF PROSTATE CANCER Info+

Dr. Sabine Mai of the Manitoba Institute of Cell Biology, CancerCare Manitoba and University of Manitoba, in collaboration with Drs. Drachenberg and Saranchuk at the Manitoba Prostate Centre, report on the use of Screencell technology for their researches on Prostate cancer.

BREAKTHROUGH IN DIAGNOSIS OF PROSTATE CANCER

WINNIPEG, MB:  Dr. Sabine Mai of the Manitoba Institute of Cell Biology, CancerCare Manitoba and University of Manitoba, in collaboration with Drs. Drachenberg and Saranchuk at the Manitoba Prostate Centre, have made advances in examining circulating tumor cells (CTCs) from the blood of prostate cancer patients. The encouraging new advancements were made possible, in part, with funds raised by the Manitoba Motorcycle Ride for Dad.

Dr. Mai, Director of the Genomic Centre for Cancer Research and Diagnosis and head of the test project, presented findings about the new blood test at a recent meeting in Boston. She co-founded 3D Signatures Inc., for commercialization of the test. “The new blood test for prostate cancer will be less invasive with a potential to be more accurate,” said Dr. Mai, who is working to get certification for the test from Health Canada.

As reported by Frank Luba in the Vancouver Province (02/03/2015), Dr. Oliver Prange (Vancouver) said the new test is focused on the intermediate group of men diagnosed with prostate cancer, which comprises about 30 per cent of the total cases. Men in the intermediate group will either receive active surveillance or aggressive cancer therapy, depending on the diagnosis. “The team looks at the structural arrangement of the chromosome component which eliminates what is a bit of a guessing game,” said Dr. Prange. “Early evidence clearly clustered patients into risk groups.  We hope to accurately predict which patients will stay indolent and which will progress,” he said.

“We hope that it will dramatically change the prognostic outlook of intermediate-risk prostate cancer patients,” said Dr. Mai.

Dr. Stuart Edmonds of Prostate Cancer Canada is encouraged by the new test. “I think it’s very promising,” Edmonds said from Toronto, where he is Prostate Cancer Canada’s vice-president of research, health promotions and survivorship. “We need to have a better test to distinguish between the aggressive disease that a man will die of rather than the more indolent, or non-aggressive disease, that a man will die with,” said Edmonds. Research is also under way to see if the new test could be used in the prognosis of other cancers, such as breast cancer, Hodgkin’s lymphoma and multiple myeloma.

Prostate cancer is the most commonly diagnosed cancer among men. It is estimated 23,600 men in Canada will be diagnosed with the cancer in 2015 and 4,000 would die from the disease.

Since 2009, over $860,000 has been raised by the Manitoba Motorcycle Ride for Dad for prostate cancer research and education. Dr. Mai’s research is proof-positive Manitobans are making a real difference. “Thank you to all Manitoba Motorcycle Ride for Dad volunteers, riders, donors and sponsors for your strong support of the project,” added Dr. Mai.

A video re: Dr. Mai’s project is found here: Dr. Sabine Mai Research Project   Visit: www.ridefordad.ca/manitoba for more information about the Motorcycle Ride for Dad.

Contacts:

Dr. Sabine Mai:                                                  (204) 787-2135  sabine.mai@umanitoba.ca

Ed Johner, Spokesperson, MRFD:                  (204) 794-5602  edjohner@icloud.com

Moe Sabourin, Co-Chair, MRFD:                    (204) 228-4301  MSabourin@wpa.mb.ca

Kirk Van Alstyne, Co-Chair, MRFD:                (204) 470-9913  kvanalstyne@winnipeg.ca

 

2014

October, 22nd
18e appel à projets FUI : Le projet Screencell “EXPEVIVO2-CTC” labellisé par le pôle de compétitivité Medicen Paris Region Info+

18e appel à projets FUI :

4 projets labellisés par le pôle de compétitivité Medicen Paris Region
Les ministres en charge de la politique des pôles de compétitivité, en lien avec les présidents des Conseils régionaux et l’association des Régions de France, ont annoncé le financement de 67 projets sélectionnés lors du 18ème appel à projets du FUI-Régions.
Ainsi, 128 projets ont été déposés à cet appel à projets, témoignant du dynamisme des écosystèmes des pôles de compétitivité dans tous les domaines. Parmi eux, les projets Bacti-DIAG, EXPEVIVO2-CTC, MARBIOTECH2 et PHOSA, tous labellisés par Medicen Paris Region.

Des cellules malignes peuvent se détacher des tumeurs et passer dans le sang où elles constituent les cellules tumorales circulantes (CTC), certaines d’entre elles étant à l’origine des métastases. Les CTC sont accessibles par une prise de sang et représentent parfois le seul matériel tumoral résiduel après traitement. Les CTC constituent l’un des axes les plus actifs de recherche sur le cancer avec plus de 400 essais cliniques incluant les CTC comme biomarqueurs. C’est pourquoi il est crucial d’anticiper la demande du marché en créant un outil disponible à court terme. La technique développée par la société ScreenCell (95), pilote du projet EXPEVIVO2-CTC, déjà testée en recherche et en clinique en France et à l’étranger apporte une solution économique pour effectuer des tests d’efficacité thérapeutique adaptés à chaque patient. Ce projet a reçu 1,5 M€ de financement pour un budget de 2,6 M€. Les partenaires de ce projet sont les unités Inserm U972 (75) et U976 (75), les sociétés IMSTAR SA (75) et Celenys (76) ainsi que le centre d’onco-dermatologie de l’Hôpital Saint Louis – AP-HP (75).

Communiqué de presse Medicen FUI-18

October, 22nd
Researchers Use ScreenCell® To Enrich Breast Cancer CTC Biomarkers Info+

Researchers Use Screencell to enrich Breast Cancer CTC Biomarkers

Researchers Use ScreenCell® To Enrich Breast Cancer CTC Biomarkers

October 22, 2014 07:30 AM Eastern Daylight Time

PARIS–(BUSINESS WIRE)–ScreenCell has entered into a collaborative study with the Jefferson Breast Care Center at the Sidney Kimmel Cancer Center of Thomas Jefferson University in Philadelphia, to evaluate the effectiveness of ScreenCell’s proprietary devices and protocols for enrichment of Circulating Tumor Cells (CTCs) from peripheral blood. ScreenCell technology separates CTCs from blood components by differential size.

“We are delighted to be working with the research team at Jefferson to help accelerate the characterization of circulating tumor cells from breast cancer patients. We are committed to help cancer researchers address these challenges.”

“Although we have utilized CTC enumeration techniques for blood samples from patients based on whether the cell is producing the EpCam marker (Epithelial Cell Adhesion Molecule) on the surface of the cell, we have shown that in 30-40% of metastatic breast cancer cases, such tests could be negative,” said Massimo Cristofanilli MD, Director of the Jefferson Breast Care Center. “These cases are especially important for us to understand due to the high mutation rate. The molecular characterization of these EpCam negative cells assessing individual gene sequence and protein expression is an important step to improve our efforts in advancing precision medicine. We are hopeful that the ScreenCell technology and enrichment protocols will enable us to achieve these research objectives.”

“Our scientists at ScreenCell Laboratories work closely with clinical research sites in order to provide the most effective customized protocols, and we have hosted Dr. Zhaomei Mu from Dr. Cristofanilli’s lab at our laboratory in Paris. We look forward to working with Dr. Cristofanilli’s entire research team,” said Georges Uzan PhD, Chief Scientific Officer at ScreenCell.

David Znaty, ScreenCell’s CEO, stated, “We are delighted to be working with the research team at Jefferson to help accelerate the characterization of circulating tumor cells from breast cancer patients. We are committed to help cancer researchers address these challenges.”

About ScreenCell

ScreenCell, headquartered in Paris, France is a privately held company dedicated to provide products, protocols and training support for cancer research facilities to characterize Circulating Tumor Cells and other rare cells in biological specimens. For more information please visit www.screencell.com

Contacts

ScreenCell
John Lindsay, 978-692-9049
Vice President, Sales and Marketing
jlindsay@screencell.com
contact@screencell.com

September, 10th
ScreenCell’s devices are dedicated to the research market and are now CE labeled for the extraction from blood of circulating tumor cells for the clinical market in Europe Info+

August, 14th
Researchers Report ScreenCell® Usage for Colorectal Cancer – CTC Biomarker Info+

Researchers Report ScreenCell® Usage for Colorectal Cancer – CTC Biomarker

August 12, 2014 08:30 AM Eastern Daylight Time

PARIS–(BUSINESS WIRE)–In a recent paper, Cancer Biomarkers (Cancer Biomarkers 14 (2014) p.145–150), researchers at Rouen University Hospital, Rome University Hospital-La Sapienza, and University of Medicine and Pharmacy, Cluj-Napoca, Romania report on the use of the ScreenCell Cyto device to capture and characterize Circulating Tumor Cells (CTCs) from patients with colorectal cancer (CRC). This is the first preliminary report on the use of ScreenCell with samples from CRC patients.

“Presence of CTCs was identified in 23/36 patients with mCRC (64%). Cytokeratin antigen was mainly lost in CTC probably due to EMT. EpCam and moreover CDX2 were detected on CTC, confirming their digestive origin.”

The authors describe the issue with using antibody capture methods for separation of CTCs: “CTCs undergo EMT (epithelial-mesenchymal transition); thus, it is important to choose the right antibody for their characterization. This finding could also explain why microfiltrating approaches seem to be more efficient than technologies based on immunomagnetic or microfluidic separation, which rely on the presence of EpCam antigen at the surface of the CTC.”

Regarding the basis of separation incorporated in ScreenCell technology: “Circulating blood cells are among the smallest cells in the body. Filtering the blood through a membrane…can eliminate them. After filtration, the remaining cells present on the membrane are then morphologically analyzed to assert their tumoral nature. This simple and rapid technique does not require expensive equipment (a single use device) and can be used easily in routine practice.”

The authors also state: “This fast and efficient method identifies CTCs and also isolates cells in EMT, which explains its high efficiency compared to technologies based on immunomagnetic and microfluidic separation reliant on EpCAM presence on the cell surface.”

Results: “Presence of CTCs was identified in 23/36 patients with mCRC (64%). Cytokeratin antigen was mainly lost in CTC probably due to EMT. EpCam and moreover CDX2 were detected on CTC, confirming their digestive origin.”

ScreenCell’s CEO David Znaty commented, “We are exceptionally pleased to learn from researchers about the results of ScreenCell for improving therapies and management of CRC cases. We are committed to help cancer researchers address these challenges.”

About ScreenCell

ScreenCell, headquartered in Paris, France is a privately held company dedicated to provide products, protocols and training support for cancer research facilities to characterize Circulating Tumor Cells and other rare cells in biological specimens. For more information please visit www.screencell.com.

Contacts

ScreenCell
John Lindsay, +1 978-692-9049
VP Marketing and Sales
jlindsay@screencell.com
contact@screencell.com

June, 24th
NYtimes: “Sidestepping the Biopsy With New Tools to Spot Cancer” By Andrew Pollack April 7, 2014 Info+

http://www.nytimes.com/2014/04/08/business/cancer-analysis-tools-circumvent-biopsies.html?_r=0

 

June, 13th
ScreenCell® Marks Shipment of 50,000 units for Characterization of Circulating Tumor Cells Info+

ScreenCell is a fully disposable, self-contained separation device that removes all blood components from CTCs, based on size differential. “We provide a customized solution to research sites that include optimum transportation of patent samples, rapid cell separation, and validated protocols for characterization.” said Georges Uzan, CSO of ScreenCell.

ScreenCell’s patented design supports a complete set of downstream analyses, including cell culture and identification of most aggressive CTC subpopulations.

 

ScreenCell Marks shipment of 50000 units !

2013

January, 15th
Paris – ScreenCell today released a white paper that details a “next generation” technology for fast isolation of undamaged fixed cells and viable live circulating tumor cells Info+

ScreenCell offers a white paper on effective circulating tumor cells isolation

 Paris– ScreenCell today released a white paper that details a “next generation” technology for fast isolation of undamaged fixed cells and viable live circulating tumor cells.

The white paper entitled Rapid and Simple isolation of Circulating Tumor Cells for Clinical and Research Applications using ScreenCell (http://www.screencell.com/wp-content/uploads/2013/01/ScreenCell-White-Paper.pdf) highlights the difficulty most systems have of effectively isolating cells and details the advantages brought by the use of non invasive handheld – independent of any equipment – innovating devices.

Most commonly used systems base CTC capture according to their expressed level of certain protein such as EpCam, this approach generates biases and does not allow the isolation of cells not expressing those specific markers as it is the case for certain types of cancer such as melanoma or pancreas, or expressing those markers but only before their epithelial – mezenchymal transition.

Size base cell selection suppresses the bias introduced by antibody based cell capture.

CTCs isolation systems, especially when they can be used as point of care devices – such as ScreenCells’ –  are the only non invasive approach allowing to:

 

  • Understand the mechanisms responsible for disease or tumor progression
  • Monitor the efficacy of targeted therapies and patients’ treatments
  • Allow earlier prediction of metastatic risks

About ScreenCell

ScreenCell was founded with the objective of designing and producing a simple but revolutionary technique allowing the fast and effective isolating of fixed and live Rare Circulating Cells yielding free of any bias CTC population amenable to better cellular and molecular characterization important in cancer monitoring. The technology also contributes to the development of a new non-invasive approach to prenatal diagnosis.

 

Contact:

Michèle Arnoe

VP Business Development

+33 (0)1 53 61 37 96

2012

July, 9th
ScreenCell and BioView Announce Worldwide Commercial Collaboration Agreement for Circulating Tumor Cell (CTC) Technology Info+

REHOVOT, Israel and PARIS, July 9, 2012

BioView Ltd. (TASE: BIOV) and ScreenCell, a privately-held company, today jointly announced the signing of a commercial collaboration agreement for Bioview’s Automated Cell Imaging Systems for imaging of CTC’s isolated with ScreenCell’s Cyto Kit ®.

Dr. Alan Schwebel, President and CEO of BioView, views this agreement as a unique combination of two innovative technologies, one designed by ScreenCell to isolate rare cells of potentially significant prognostic and predictive value in cancer, and another, BioView’s scanning platform, which provides automated imaging and analysis solutions for rare cell and circulating tumor cell detection. “BioView’s unique automated imaging and analysis solutions for the detection and of rare cells greatly enhance research and clinical laboratory productivity and assay development process. We are proud to be ScreenCell’s global partner and look forward to expanding our relationship.”

Bioview’s Imaging Systems are designed to accommodate both the need for CTC enumeration and retrieval of cellular and marker characteristics of captured cells. Utilizing field-proven algorithms developed and perfected in collaboration with leading cancer research centers worldwide, BioView’s scanning platform is the ideal solution for both clinical and research laboratories wishing to enhance their productivity and assay development processes.

ScreenCell offers innovative, single-use devices to isolate by size and characterize a wide variety of tumor cells, both live and fixed, including mesenchymal cells, cancer stem cells, microembolii and cancer cells of non-epithelial origin. These cells, which are considered to be important in metastasis, are often not captured or cannot be sensitively detected through existing technologies that only target cells expressing EpCam, a transmembrane glycoprotein on epithelial cells. With the ScreenCell devices, collected cells are also well preserved morphologically and can be isolated and grown in culture for drug screening or further genomics analysis.

“Our goal in designing ScreenCell technologies was to create a universal system, not limited to detection of cells of non-epithelial origin and free of any bias potentially linked to the use of antibodies for cell capture,” stated David Znaty, Chief Executive Officer of ScreenCell. “Our objective is to support a breakthrough in personalized medicine by creating a non-invasive evaluation of specific therapeutic targets and ‘real time’ monitoring of target evolution which we strongly believe will be facilitated by combining ScreenCell and BioView technologies.”

About BioView Ltd.

Established in 2000, and led by an expert team of biologists, software engineers and physicists, BioView develops, manufactures and supplies cell imaging equipment, biological kits and software to medical institutes and universities.  BioView is a publicly traded company on the Israeli Stock exchange, and currently has strategic collaborations underway with international scientific leaders and institutions. For more information about the BioView technology, and press related issues, please contact alan@bioview.co.il or visit our website at http://www.bioview.co.il.

About ScreenCell

ScreenCell was founded with the objective of designing and producing a simple but revolutionary technique allowing the fast and effective filtering of Rare Circulating Cells yielding high-quality CTC population amenable to better cellular and molecular characterization.

ScreenCell designed a full range of point of care devices for development for use in in vitro Diagnostics (IVD) assays and platforms.

ScreenCell is dedicated to creating technologies allowing CTCs to become potential end points in future oncology therapeutic arsenals by filtering out healthy live tumor cells, thus enabling:

  • molecular biology
  • cell culture
  • enumeration and cytomorphology evaluation

 

Contact Information:

BioView Dr. Alan Schwebel President and CEO  Tel:  +972-8-936-6868 alan@bioview.co.il

ScreenCell David Znaty CEO  +33(0)1-53-61-91-33 dznaty@screencell.com

May, 17th
Affymetrix and ScreenCell Announce Worldwide Distribution Agreement for Circulating Tumor Cell (CTC) Technology Info+

Affymetrix and ScreenCell Announce Worldwide Distribution Agreement for Circulating Tumor Cell (CTC) Technology

Affymetrix releases first CTC platform for 4-color RNA-ISH

Combination of ScreenCell’s isolation devices and Affymetrix’ QuantiGene® ViewRNA ISH technology enables easy, accessible, sensitive, multiplex, low-cost system to enumerate and characterize CTCs and other rare cells.

 

SANTA CLARA,Calif., &PARIS,France– May 17, 2012 – Affymetrix, Inc. (NASDAQ: AFFX) and ScreenCell, a privately-held company, today announced the signing of a worldwide distribution agreement for ScreenCell’s isolation devices and dilution buffers,* designed for the collection of Circulating Tumor Cells (CTCs) in peripheral blood.

The agreement makes Affymetrix the exclusive distributor of ScreenCell® products* used in combination with in situ hybridization (ISH) assays, microarray assays, and other non-PCR based nucleic acid assays including Affymetrix’ industry-leading QuantiGene® ViewRNA Assays,* QuantiGene® Plex Assays,* and GeneChip® Microarray Assays.* The QuantiGene® ViewRNA CTC platform, consist of ScreenCell’s products and Affymetrix’ QuantiGene ViewRNA Assays, is now available from Affymetrix.

“This agreement is a powerful combination of two innovative technologies, one designed to isolate rare cells of potentially significant prognostic and predictive value in cancer, and another, our QuantiGene ViewRNA ISH Cell Assays, designed to detect single RNA transcripts in single CTCs and rare cells with high specificity,” stated George Bers, Vice President & General Manager, Expression Business Unit – Panomics for Affymetrix. “Today we are launching our CTC platform, which combines our highly sensitive and specific QuantiGene ViewRNA Assay with ScreenCell’s isolation devices. We believe this platform may potentially have a dramatic impact on disease detection, enabling researchers in translational sciences to further examine the impact on treatment, management and outcome in cancer. We are proud to be ScreenCell’s global partner and look forward to releasing additional assays and research applications.”

ScreenCell offers innovative, single-use devices to isolate by size and characterize a wide variety of tumor cells, both live and fixed, including mesenchymal cells, cancer stem cells, microembolii and cancer cells of non-epithelial origin. These cells, which are considered to be important in metastasis, are often not captured or cannot be sensitively detected through existing technologies that only target cells expressing EpCam, a transmembrane glycoprotein on epithelial cells. With the ScreenCell devices, collected cells are also well preserved morphologically and can be isolated and grown in culture for drug screening or further genomics analysis.

“Our goal in designing ScreenCell® technologies was to create a universal system, not limited to detection of cells of non-epithelial origin and free of any bias potentially linked to the use of antibodies for cell capture,” stated David Znaty, Chief Executive Officer of ScreenCell. “Our goal is to provide a technology to support further research for use in personalized medicine by creating a broadly accessible, non-invasive evaluation of specific, potential therapeutic targets. We are excited to work with Affymetrix not just for their commercial strength, but because we believe strongly in our combined technologies.”

* “For Research Use Only. Not for use in diagnostic procedures.”

PLEASE NOTE: Affymetrix®, the Affymetrix logo, GeneChip®, and QuantiGene® are registered trademarks of Affymetrix, Inc. All other trademarks are the property of their respective owners.

About ScreenCell

ScreenCell was founded with the objective of designing and producing a simple but revolutionary technique allowing the fast and effective filtering of Rare Circulating Cells yielding high-quality CTC population amenable to better cellular and molecular characterization.

ScreenCell designed a full range of point of care devices for development for use in in vitro Diagnostics (IVD) assays and platforms.

ScreenCell is dedicated to creating technologies allowing CTCs to become potential end points in future oncology therapeutic arsenals by filtering out healthy live tumor cells, thus enabling:

  • molecular biology
  • cell culture
  • enumeration and cytomorphology evaluation

For more information about ScreenCell, please visit www.screencell.com.

About Affymetrix

Affymetrix technology is used by the world’s top pharmaceutical, diagnostic, and biotechnology companies, as well as leading academic, government, and nonprofit

research institutes. More than 25,000 peer-reviewed papers have been published using the technology. Affymetrix is headquartered in Santa Clara, Calif., and has manufacturing facilities in Santa Clara, Cleveland, Ohio, and Singapore. The company has about 900 employees worldwide and maintains sales and distribution operations across Europe, Asia, and Latin America. For more information about Affymetrix, please visit www.affymetrix.com.

Forward-looking statements

All statements in this press release that are not historical are “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act as amended, including statements regarding Affymetrix’ “expectations,” “beliefs,” “hopes,” “intentions,” “strategies” or the like. Such statements are subject to risks and uncertainties that could cause actual results to differ materially for Affymetrix from those projected. These and other risk factors are discussed in Affymetrix’ Form 10-K for the year ended December 31, 2011, and other SEC reports for subsequent quarterly periods.

Affymetrix, Inc.

Media Contact:

Mindy Lee-Olsen

Vice President, Marketing Services

+(1) 408-731-5523

mindy_lee-olsen@affymetrix.com

 Investor Contact:

Doug Farrell

Vice President, Investor Relations

+(1) 408-731-5285

doug_farrell@affymetrix.com

 ScreenCell

Media Contact:

David Znaty

CEO

+33 (0) 1 53 61 91 33

contact@screencell.com

2011

November, 8th
Transgenomic and ScreenCell Announce Worldwide Distribution and Collaboration Agreement for Circulating Tumor Cell (CTC) Technology Info+

Transgenomic and ScreenCell Announce Worldwide Distribution and Collaboration Agreement for Circulating Tumor Cell (CTC) Technology

OMAHA, Neb. & PARIS–(BUSINESS WIRE)–Transgenomic, Inc. (OTC/BB: TBIO) and ScreenCell, a privately- held company, today announced the signing of a perpetual, worldwide collaboration and distribution agreement for ScreenCell’s Isolation Devices and Dilution Buffers, designed for the collection of Circulating Tumor Cells (CTCs) in peripheral blood. ScreenCell® offers innovative, single-use devices to isolate by size and characterize all possible tumor cells, including mesenchymal cells. Mesenchymal cells, thought to be cancer stem cells important in cancer assessment, are not collected through technologies that only target cells expressing EpCam, a transmembrane glycoprotein on epithelial cells. Their collection is therefore a key advantage of ScreenCell’s technologies. Collected cells are also well preserved morphologically, allowing isolation of live cells able to grow in culture and collection of high quality genetic materials.

The agreement makes Transgenomic the exclusive distributor of ScreenCell technologies used in combination with Transgenomic’s industry leading high-sensitivity mutation detection products, including its ICE COLD-PCR assays, BLOCker-Sequencing cancer mutation assays, SURVEYOR Scan cancer mutation kits and WAVE instrument systems. The Company expects to begin selling ScreenCell products immediately, in combination with Transgenomic technology, as part of its pharmacogenomic services and for other, non-exclusive broad research applications to drug developers and academic centers.

“This agreement is an important marriage of technologies, one designed to isolate rare cells of potentially significant prognostic value in cancer, and another, our ICE-COLD PCR, designed to enrich mutations to levels that can be detected even in small CTC cell loads and amidst competing wild-type DNA,” stated Craig Tuttle, President and Chief Executive Officer of Transgenomic. “In the longer-term, we look forward to offering CTC collection as a combined kit product with our ICE-COLD PCR kits. Combined again with our ultra high-sensitivity genetic variation and mutation analysis capabilities, we believe this platform may have a dramatic impact on disease detection, treatment, management and outcome in cancer. We are proud to be ScreenCell’s first global partner and look forward to our validation work with these technologies.”

“Our goal in designing ScreenCell technologies was to create a universal system, not limited to detection of cells of nonepithelial origin and free of any bias potentially linked to the use of antibodies for cell capture,” stated David Znaty, Chief Executive Officer of ScreenCell. “Our goal is to support a breakthrough in personalized medicine by creating a non-invasive evaluation of specific therapeutic targets and ‘real time’ monitoring of target evolution under the pressure of targeted therapies in cancer. We are excited to work with Transgenomic not just for their commercial strength, but because we believe strongly in our combined technologies.”

Both companies have agreed to support the development of the combined technologies which, to date, have been tested in a proof of concept study at the Dana Farber Cancer Institute. Transgenomic and ScreenCell plan additional validation efforts with Dana Farber and other key researcher institutions to further establish the ability to isolate CTCs and, using the combined products, find new marker genes which may be involved in early diagnostic as well as mutations involved in determining, prognosis and therapeutic response. Transgenomic plans to begin the validation process for the combined products immediately, with the goal of commercializing such an offering for clinical trial use.

About Transgenomic

Transgenomic, Inc. (www.transgenomic.com) is a global biotechnology company advancing personalized medicine in cancer and inherited diseases through its proprietary molecular technologies and world-class clinical and research services. The Company has three complementary business divisions: Transgenomic Pharmacogenomic Services is a contract research laboratory that specializes in supporting all phases of pre- clinical and clinical trials for oncology drugs in development. Transgenomic Clinical Laboratories specializes in molecular diagnostics for cardiology, neurology, mitochondrial disorders, and oncology. Transgenomic Diagnostic Tools produces equipment, reagents, and other consumables that empower clinical and research applications in molecular testing and cytogenetics. Transgenomic believes there is significant opportunity for continued growth across all three businesses by leveraging their synergistic capabilities, technologies, and expertise. The Company actively develops and acquires new technology and other intellectual property that strengthen its leadership in personalized medicine.

About ScreenCell

ScreenCell was founded with the objective of designing and producing a simple but revolutionary technique allowing the fast and effective filtering of Rare Circulating Cells yielding high quality CTC population amenable to better cellular and molecular characterization.

ScreenCell designed a full range of point of care devices compatible with existing In vitro Diagnostics (IVD) assays and platforms, with no need for any interface development.

ScreenCell is dedicated to creating technologies allowing CTCs to become potential end points in future oncology therapeutic arsenals, by filtering out healthy live tumor cells, thus enabling:

. molecular biology

. cell culture

. enumeration and cytomorphology evaluation

The technology has also demonstrated its advantages for the isolation of Circulating Fetal Cells (CFCs) drawn from peripheral blood of pregnant women, potentially leading to a significantly facilitated and cost-effective process for prenatal diagnosis of genetic diseases.

Forward-Looking Statements for Transgenomic

Certain statements in this press release constitute “forward-looking statements” of Transgenomic within the meaning of the Private Securities Litigation Reform Act of 1995, which involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Forward-looking statements include, but are not limited to, those with respect to management’s current views and estimates of future economic circumstances, industry conditions, company performance and financial results, including the ability of the Company to grow its involvement in the diagnostic products and services markets. The known risks, uncertainties and other factors affecting these forward-looking statements are described from time to time in Transgenomic’s filings with the Securities and Exchange Commission. Any change in such factors, risks and uncertainties may cause the actual results, events and performance to differ materially from those referred to in such statements.

Accordingly, the Company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 with respect to all statements contained in this press release. All information in this press release is as of the date of the release and Transgenomic does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

Contacts

Transgenomic Contact

Investor Relations, 402-452-5416

investorrelations@transgenomic.com

or

ScreenCell Contact

Michèle Arnoe, +33 1 53 61 37 96

VP Marketing & Business Development

marnoe@screencell.com

or

Investor Contact

Argot Partners

David Pitts, 212-600-1902

david@argotpartners.com

March, 28th
A New Device for Rapid Isolation by Size and Characterization of Rare Circulating Tumor Cells Info+

Abstract. Background: Circulating tumor cells (CTCs) likely derive from clones in the primary tumor, suggesting that they can be used for all biological tests applying to the primary cells. Materials and Methods: The ScreenCell® devices are single-use and low-cost innovative devices that use a filter to isolate and sort tumor cells by size. Results: The ScreenCell® Cyto device is able to isolate rare, fixed, tumor cells, with a high recovery rate. Cells are well preserved morphologically. Immunocytochemistry and FISH assays can be performed directly on the filter. The ScreenCell® CC device allows isolation of live cells able to grow in culture. High quality genetic materials can be obtained directly from tumor cells isolated on the ScreenCell® MB device filter. Conclusion: Due to their reduced size, versatility, and capacity to isolate CTCs within minutes, the ScreenCell® devices may be able to simplify and improve non-invasive access to tumor cells.

Read the full article : http://www.iiar-anticancer.org/openAR/journals/index.php/anticancer/index

 

ISABELLE DESITTER1*, BELLA S. GUERROUAHEN1*, NAOUAL BENALI-FURET1*,

JANINE WECHSLER1, PASI A. JANNE2, YANAN KUANG3, MASAHIKO YANAGITA3,

LILIN WANG3, JILLIAN A. BERKOWITZ3, ROBERT J. DISTEL3 and YVON E. CAYRE1,4

1ScreenCell, 75012 Paris, France;

2Medical Oncology/Solid Tumor Oncology and 3Translational Research Laboratory,

Center For Clinical and Translational Research, Dana-Farber Cancer Institute, Boston MA 02115, U.S.A.; 4Hôpital Robert Debré and Pierre and Marie Curie University, 75019 Paris, France


 

March, 28th
Melanoma Initiating Cells and Circulating Melanoma Cells: a Blurred Picture Info+

Whether a subset of tumorigenic cancer stem cells* exist in human melanomas remains a controversial issue though it is of critical importance in order since treatments which may eliminate the undifferentiated subset of cancer cells may cure patients (1,2). Therefore, it will be critical to identify cancer cells that have the tumorogenic potential in patients, in order to develop more effective targeting therapies.

Positive View.

Taking patient melanoma tumors from a broad spectrum of sites and stages, Boiko et al. (3) showed that in melanomas, tumor stem cells could be isolated as a highly enriched CD271+ population. Indeed, transplantation of highly viable FACS isolated melanoma cells resuspended in a Matrigel® into T, B, and NK deficient Rag2−/− γc−/− mice, resulted in melanoma from CD271+ but not CD271 cells. The authors also showed that tumors transplanted by CD271+ patient cells were capable of metastasis in-vivo; these cells lacked expression of TYR, MART and MAGE in 86%, 69% and 68% of melanoma patients respectively.

Schatton et al. (4) found that 1 in 120,735 (0.00083%) ABCB5+ metastatic melanoma cells formed tumours in NOD/SCID mice, a tenfold enrichment over unfractionated cells. In mice grafted with human cells, the researchers found that melanoma cells expressing ABCB5 [ATP-binding cassette, sub-family B (MDR/TAP), member 5, which mediates melanoma doxorubicin resistance via its function as a doxorubicin efflux transporter], had much greater tumorigenicity than the more abundant ABCB5 cells. ABCB5+ cells were capable of self-renewal and differentiation, giving rise to both ABCB5+ and ABCB5 cells. ABCB5cells, by contrast, only generated more ABCB5 cells. Treatment of grafted mice with an anti-ABCB5 monoclonal antibody inducing cell-mediated cytotoxicity against ABCB5+ cells inhibited tumor growth.

Negative View

Such results were not confirmed by Quintana et al. (5). The authors investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and non-tumorigenic cells or whether most melanoma cells retain tumorigenic capacity, irrespective of their phenotype. They found 28% of single melanoma cells obtained directly from patients of all stages formed tumors in NOD/SCID IL2Rγ(null) mice (lacking the interleukin-2 gamma receptor as wall as natural killer cells which may eliminate many of the transplanted cancer cells in the standard NOD/SCID mice). All tumorigenic cells appeared to have unlimited tumorigenic capacity on serial transplantation, and the authors were unable to find any large subpopulation of melanoma cells that lacked tumorigenic potential. None of 22 heterogeneously expressed markers, including CD271 and ABCB5, enriched tumorigenic cells. Some melanomas metastasized in mice, irrespective of whether they arose from CD271 or CD271+ cells. Many markers appeared to be reversibly expressed by tumorigenic melanoma cells.

To assess whether tumorigenic melanoma cells are phenotypically distinct from melanoma cells that fail to form tumours, the authors examined the expression of more than 50 surface markers on melanomas, including A2B5, c-kit, CD44, CD49B, CD49D, CD49f, CD54, CD133, CD166, E-cadherin, HNK-1, L1CAM, MCAM, N-cadherin and p75 which were heterogeneously expressed by melanoma cells from multiple patients and were tested for the ability to distinguish tumorigenic from non-tumorigenic melanoma cells in vivo. In every case, tumours arose from all fractions of cells. The authors found no marker that distinguished tumorigenic from non-tumorigenic cells

Possible Clues

Adapting xenotransplantation protocols ?

Most human cancers have only rare (< 0.1%) cancer-initiating cells when transplanted into NOD/SCID or other highly immunocompromised mice (4, 6-14).Therefore, a critical question is whether optimization of xenotransplantation assays could reveal that some human cancers actually have very common cells with tumorigenic potential despite only having rare tumorigenic cells in NOD/SCID mice.

Though ABCB5 expression has been shown to correlate with the expression of CD166 and CD133 (15), Quintana et al. (16) found that CD166 or CD133 could not enrich tumorigenic melanoma cells in the modified xenotransplantation assay, raising the possibility that markers that enrich rare cells with tumorigenic potential in NOD/SCID mice may fail to distinguish tumorigenic from nontumorigenic cells in NOD/SCID Il2rg2/2 mice assays that detect much higher frequencies of tumorigenic cells. More generally, these authors showed that some cancers that appear to have rare tumorigenic cells in NOD/SCID mice actually have very common cells with tumorigenic capacity under modifications of xenotransplantation assays. Though, the authors observed a high percentage of melanoma cells that have the potential to proliferate extensively and form new tumours, it is possible that an even greater, or a much smaller, fraction of melanoma cells actually contributes to disease progression in patients.

Looking for Tumour Initiating Cells among Circulating Melanoma Cells (CMCs)?

In many neoplastic diseases, the presence of CTCs attracts considerable attention as a potential non-invasive approach prognostic and potentially predictive marker of treatment efficiency and monitoring. Though CTCs have been included into the international tumor staging systems for several carcinomas, it is not as yet the case for melanoma (17,18). Circulating Tumor Cells have been described with phenotypic and genotypic similarities to cancer stem cells (19-26). It is likely that the presence of tumor initiating cells among CMCs would have a significant impact on prognosis.

Three studies addressed the possible impact of the number of enriched CMCs on prognosis. In a prospective study by Ulmer et al. (27), 50 ml blood samples were drawn from 164 patients affected by cutaneous melanoma (29 stage I, 30 stage II, 42 stage III, 63 stage IV). CMCs were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. Positivity for immunomagnetic melanoma cell enrichment correlated with the presence of detectable tumor, and detection of more than one melanoma cell in stage III or IV patients was associated with a significantly decreased overall survival. On the contrary, another study from the same group showed no significant difference between number of melanoma cells and established prognostic parameters in a cohort of patients

De Giorgi et al. (28) and Xu et al. (29) showed that analysis of circulating tumor cells (CTC) in the peripheral blood of cutaneous melanoma patients provides information on the metastatic process. Indeed, CTCs were shown in 29% of patients with primary invasive melanoma and in 62.5% of metastatic melanoma patients.

Rao et al. (30) enumerated CMCs in patients with metastatic melanoma. For that, circulating melanoma cells were immunomagnetically enriched from 7.5 ml of blood, fluorescently labelled with DAPI and identified as CD146+, HMW-MAA+ (High-molecular weight melanoma-associated antigen), CD45- and CD34-. Thirty to one hundred of CMCs expressed the proliferation marker Ki67. Such cells ranged from 0 to 8,042 per 7.5 ml, and patients with 2 CMCs per 7.5 ml of whole blood had a shorter overall survival as compared with the group with <2 CMCs.

Whether some CTCs subpopulation(s) have tumorogenic capacity is of critical importance since cancer treatments may be unsuccessful if they fail to target the specific minority subpopulation of tumour cells that have tumour initiation capacity (31-34).

*‘Cancer Stem Cells’ (35,36) are tumor cells with stem cell characteristics responsible for tumor progression; they are also known as Tumor Initiating Cells (TICs) (37).

 

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January, 27th
ScreenCell and the Caudius Regaud Cancer Institute start a new Partnership Info+

ScreenCell and the Caudius Regaud Cancer Institute ( Toulouse , France ) are collaborating on the use of the ScreenCell technology for capturing and characterizing circulating tumor cells from patient blood samples. The partners will explore primarily the possibility of monitoring targeted therapy in patients with lung cancer. They expect their collaboration to contribute to the development of personalized treatment of patients and to be an asset to the process of drug discovery

2010

November, 11th
Personalized Medicine: Crizotinib, a New Targeted Therapy in Non–Small-Cell Lung Cancer Info+

Personalized Medicine: Crizotinib, a New Targeted Therapy in Non–Small-Cell Lung Cancer.

Anaplastic lymphoma kinase (ALK) is an orphan receptor tyrosine kinase first identified as part of the t(2;5) chromosomal translocation associated with most anaplastic large cell lymphomas (ALCL) and a subset of T-cell non-Hodgkins lymphomas. The deregulated expression of full length ALK and ALK fusions has recently been observed in several nonlymphoid neoplasms.

A subset of Non-Small-Cell lung Cancers (NSCLCs) harbor a transforming echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusions , The truncated EML4 protein retains a coiled-coil oligomerization domain allowing dimerization. EML4-ALK translocations seems to be a rare aberration, most common in Asian nonsmokers or light-smokers with the adenocarcinoma subtype of NSCLC, forming a distinct subgroup from patients harboring EGFR, KRAS, or NKX2-1 aberrations. The initial frequency of EML4-ALK fusion transcripts was approximately 6.7% in Japanese NSCLC tumor samples, but subsequent studies showed lower frequencies of 3% or less. Direct demonstration of EML4-ALK as a dominant oncogenic driver in NSCLC included transformation of mouse 3T3 fibroblastic cells with forced overexpression of human EML4-ALK and de novo lung adenocarcinoma formation in mice engineered to express EML4-ALK targeted to the lung alveolar epithelial compartment.

Inflammatory myofibroblastic tumor (IMT) is a rare tumors of mesenchymal origin that arises in multiple tissues, possesses metastatic potential, and is only minimally responsive to conventional chemotherapy or radiation therapy. IMT is associated with various ALK translocations, including TPM3-ALK and TPM4-ALK, CARS-ALK, and CLTC, but not to date with fusion partners seen in NSCLC.

Crizotinib inhibits the anaplastic lymphoma kinase (ALK) gene’s receptor, tyrosine kinase, which has been linked to several types of cancer. Indeed, more than half of selected patients with advanced NSCLC responded to treatment with crizotinib, according to findings of a phase I multicenter clinical trial reported in the Oct. 28 issue of the New England Journal of Medicine. Dr. Kwak and her colleagues of Massachusetts General Hospital Cancer Center, Boston found that NSCLC with ALK rearrangements – which occurred in approximately 5% of the patients screened for participation in this trial – were highly sensitive to ALK kinase inhibition.

In a group of 82 patients, many of whom had undergone numerous anticancer therapies for advanced ALK-positive tumors, the overall partial and complete response rate was 57% (10% response rate seen in similar cancers treated with second-line multiagent chemotherapy) and disease stabilized in an additional 33%.

The probability of 6-month progression-free survival was estimated to be 72% with crizotinib therapy (at a maximal dose of 250 mg twice daily) , compared with a rate of 27% for similar tumors treated with second-line chemotherapy. Treatment response was quite rapid, with a disease-control rate of 87% at 8 weeks. Adverse effects were mild.

Two separate case reports were published in the same issue of the journal with crizotinib therapy. In the first one Dr. Young Lim Choi of Jichi Medical University, Tochigi, Japan, and associates suggested that de novo mutations may arise within the kinase domain of the ALK gene. Whether the resistant clones were present initially or developed secondarily, during treatment has not been determined. Such result strongly emphasize that further research should be devoted to the development of ALK inhibitors addressing the mutations and the resistance. Indeed, a number of such drugs are in the pipeline, including a new ALK inhibitor.

In another study, Dr. James E. Butrynski of the Dana-Farber Cancer Institute, Boston, and his associates treated two patients with IMT with crizotinib in December 2008. One patient responded to the treatment and has maintained complete radiographic remission until present time. The second patient did not respond to crizotinib, showing continued disease progression. Further analysis showed that the tumor in patient 1 had ALK rearrangements while that in patient 2 did not. Together, these two cases indicate that crizotinib is effective only in those IMTs with ALK rearrangements.

Bengt Hallberg, Ph.D., and Ruth H. Palmer, Ph.D., wrote in an editorial that in groups of patients with cancers in which ALK is implicated, a standard genotyping approach will be important for a more personalized therapeutic protocol.

Dr. Kwak and colleagues note that mutations or translocations of the ALK gene also have been implicated in anaplastic large-cell lymphoma and neuroblastoma. The latter, a devastating childhood cancer in which ALK mutations have been reported in approximately 10% of cases, makes a particularly attractive target for crizotinib, especially in view of the drug’s tolerability during long-term use in these phase I studies.

Selected References :

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703.

Butrynski JE, D’Adamo DR, Hornick JL, Dal Cin P, Antonescu CR, Jhanwar SC, Ladanyi M, Capelletti M, Rodig SJ, Ramaiya N, Kwak EL, Clark JW, Wilner KD, Christensen JG, Jänne PA, Maki RG, Demetri GD, Shapiro GI. Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010 Oct 28;363(18):1727-33.

Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H; ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010 Oct 28;363(18):1734-9.

Schönherr C, Yang HL, Vigny M, Palmer RH, Hallberg B. Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells. Oncogene. 2010 May 13;29(19):2817-30.

See also:

Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, Solomon B, Stubbs H, Admane S, McDermott U, Settleman J, Kobayashi S, Mark EJ, Rodig SJ, Chirieac LR, Kwak EL, Lynch TJ, Iafrate AJ. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009 Sep 10;27(26):4247-53.

Elsevier Global Medical News by Mary Ann Moon (Wednesday, October 27, 2010) from which the above text has been derived

Note:

According to the Oct 28 2010  New York Times , Pfizer plans to submit crizotinib to the Food and Drug Administration in the first half of next year at the same time that it submits a FISH gene diagnostic test being developed with Abbott to identify patients most likely to benefit from the drug.

November, 10th
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