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ISET®: a life commitment for improving the life of cancer patients.

The ISET® technology is the fruit of 20 years of research of Prof. Patrizia Paterlini-Bréchot and her team at the University Paris Descartes and INSERM (Institut National de la Santé et de la Recherche Médicale). Patrizia Paterlini-Bréchot is a Professor of Cellular and Molecular Biology at the University Paris Descartes in Paris, France and Hospital Practitioner at Assistance Publique-Hôpitaux de Paris. As an Oncologist and Hematologist, she and her team have studied cancer since 1982, and more specifically circulating tumor cells since 1995. The work of the team in fundamental and applied research led to the publication of high level scientific studies in the field of predictive oncology. Oncology is the science devoted to the study and treatment of cancer. Predictive Oncology is the branch of Oncology, which predicts how and when a patient has to be treated in order to better fight against cancer.

In 2000, the work of Prof. Patrizia Paterlini-Bréchot’s team led to the invention of the ISET® technology: the first and still unparalleled filtration method for isolation of  the very rare Circulating Tumor Cells (CTC) from blood, allowing their diagnostic identification by cytopathology and their molecular characterization. Once these cells are diagnostically validated by cytopathology after isolation by the ISET® technology, they are referred to as CCC, Circulating Cancer Cells.

The ISET® technology promises to improve the span and quality of life of patients with cancer. Such a highly sensitive technology will allow for a non-invasive, reliable and predictive diagnostic, which will bring remarkable help to people around the world in their struggle against cancer and save millions of lives through the early diagnosis of invasive cancers.

First patent

Vertical filtration to isolate Circulating Tumor Cells (still incomplete at this point)

ISET® defined for the first time

ISET® technology first reported in the American Journal of Pathology by Professor Paterlini-Brechot’s team

Publication

Vona G. et al
Am J Pathol 2000 Jan;156(1):57-63.
ISET, Isolation by Size of Epithelial Tumor cells: a new method for isolation, immunomorphological and molecular characterization of circulating tumor cells

First patent

Vertical blood filtration

Founding of Metagenex

First company founded to develop and commercialize the ISET® technology based on the exclusive licensing of patents belonging to the French public institutions University Paris Descartes, Assistance Publique Hôpitaux de Paris and INSERM.

Second patent

NI-PND: Non-Invasive Prenatal Diagnosis

Publication

Vona G. et al
Am J Pathol, 2002 Jan;160(1):51-8.
Enrichment and genetic analyses of fetal cells circulating in the maternal blood by the ISET technique and single cell microdissection : a non-invasive tool for early prenatal diagnosis

Publication

Béroud C. et al
Lancet, 2003 Mar 22;361(9362):1013-4.
Prenatal diagnosis of Spinal Muscular Atrophy (SMA) by genetic analysis of circulating fetal cells

Publication

Vona G. et al
Hepatology 2004 Mar;39(3):792-7.
Impact of cytomorphological and molecular characterization of circulating tumor cells in patients with Primary Liver Cancer

Publication

Lelièvre L. et al
Int J Gynecol Cancer 2004 Mar-Apr;14(2):229-33.
Effect of laparoscopy versus laparotomy on circulating tumor cells using isolation by size of epithelial tumor cells

Production

Manufacturing of ISET® device and consumables

Third patent

Vertical filtration, device and consumables

Fourth patent

NI-PND (non invasive prenatal diagnosis) of cystic fibrosis

Development of scientific recognition

Publication

Pinzani P. et al
Hum Pathol. 2006 Jun;37(6):711-8.
Isolation by size of epithelial tumor cells in peripheral blood of patients with breast cancer: correlation with real time reverse transcriptase-polymerase chain reaction results and feasibility of molecular analysis by laser microdisection

Publication

Saker A. et al
Prenat Diagn. 2006 Oct;26(10):906-16.
Genetic characterization of circulating fetal cells allows non invasive prenatal diagnosis of cystic fibrosis (CF).

Publication

Paterlini-Bréchot P. et Benali N.
Cancer Lett. 2007 Aug 18;253(2):180-204
Circulating Tumor Cells (CTC) detection: Clinical impact and future directions

Rarecells SAS is born

Rarecells SAS is born and the team gets a US federal grant for oncology and a grant for NI-PND

Production

Manufacturing of Rarecells device and consumables and improvement of filters and buffers.

Award

Patrizia Paterlini-Brechot is awarded the prestigious AP-HP (Assistance Publique – Hôpitaux de Paris) award for NI-PND.

Publication

Pinzani P. et al
Melanoma Res. 2010 Aug;20(4):303-10.
Tyrosinase mRNA levels in the blood of uveal melanoma patients: correlation with the number of circulating tumor cells and tumor progression

Publication

Descamps V. et al
Arch Dermatol 2010 Oct;146(10):1156-7.
ISET device: a useful tool to answer some questions about the biologic behavior of melanocytic nevus cells

Publication

De Giorgi V. et al
J Invest Dermatol. 2010 Oct;130(10):2440-7 2010
Application of a filtration and isolation-by-size technique for the detection of criculating tumor cells in cutaneous melanoma. J Invest Dermatol

Publication

De Giorgi V. et al
Arch Dermatol. 2010 Oct;146(10):1120-4.
Circulating benign nevus cells detected by ISET technique: warning for melanoma molecular diagnosis.

Foundation

Foundation of Rarecells Holdings and Rarecells subsidiaries. Rarecells® and ISET ® trademarks are deposited.

Publication

Hofman V. et al
Am J Clin Pathol, 2011 Jan;135(1):146-56.
Cytopathologic Detection of Circulating Tumor Cells Using the Isolation by Size of Epithelial Tumor Cell Method.

Publication

Hofman V. et al
Clin Cancer Res 2011 Feb 15;17(4):827-35
Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker

Publication

Hou JM. et al
Am J Pathol, 2011 Mar;178(3):989-96.
Circulating Tumor Cells as a Window on Metastasis Biology in Lung Cancer

Publication

Eifler et al.
Cytometry Part B 2011, 80B: 100-111
Enrichment of circulating tumor cells from a large blood volume using leukapheresis and elutriation: Proof of concept.

Publication

Paterlini-Bréchot P.
Future Oncol. 2011 Jul;7(7):849-71.
Organ-specific markers in circulating tumor cell screening: an early indicator of metastasis-capable malignancy.

Publication

Farace et al.
Br J Cancer. 2011 Sep 6;105(6):847-53
A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas.

Publication

Hofman V. et al
Int J Cancer, 2011 Oct 1;129(7):1651-60
Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small cell lung carcinoma: Comparison of the efficacy of the CellSearch AssayTM and the isolation by size of epithelial tumor cell method

Publication

Lecharpentier et al.
Br J Cancer. 2011 Oct 25; 105(9): 1338–1341
Detection of circulating tumor cells with an hybrid (i.e. epithelial/mesenchymal) phenotype in patients with metastatic non-small celll lung cancer.

Publication

Khoja et al.
Br J Cancer. 2012 Jan 31; 106(3):508-16. Epub 2011 Dec 20
A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker.

Publication

Hou et al.
J Clin Oncol. 2012 Feb 10;30(5):525-32, Epub 2012 Jan 17
Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer.

Publication

Krebs et al.
J Thorac Oncol. 2012;7: 306–315
Analysis of Circulating Tumor Cells in Patients with Non-small Cell Lung Cancer Using Epithelial Marker-Dependent and -Independent Approaches

Publication

Hofman V. et al
Cytopathology 2012 Feb;23(1):30-8.
Morphological analysis of circulating tumor cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumor cell (ISET) method.

Fifth Patent

Rare Cells extraction from biological fluids and multiplexing

Publication

Ilie. et all
Ann Oncol. 2012 Nov;23(11):2907-13, Epub 2012 Jun 26
ALK-gene rearrangement: a comparative analysis on circulating tumour cells and tumour tissue from patients with lung adenocarcinoma.

Publication

Hofman et al.
Journal of Investigative Dermatology (2013) 133, 1378–1381; published online 10 January 2013
Usefulness of Immunocytochemistry for the Detection of the BRAF V600E Mutation in Circulating Tumor Cells from Metastatic Melanoma Patients

R&D

Development of R&D for molecular theranostics

Publication

Pailler et al.
J Clin Oncol. 2013 Jun 20;31(18):2273-81
Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non–small-cell lung cancer.

Publication

Costa, D.
Journal of Clinical Oncology, 31(18) 2013: pp 2236-223
Identification of Somatic Genomic Alterations in Circulating Tumors Cells: Another Step Forward in Non–Small-Cell Lung Cancer?

Publication

Marchesi, V.
Nat Rev Clin Oncol. 2013 Jul;10(7):366.
Lung cancer: ALK status of NSCLC reflected in CTCs.

Publication

Ma, Y.C. et al
Technol Cancer Res Treat. 2013 Aug;12(4):295-309.
Recent Advances and Prospects in the Isolation by Size of Epithelial Tumor Cells (ISET) Methodology

Publication

Chinen et al.
J Thorac Dis. 2013 Oct; 5(5): 593–599
Cytokeratin-based CTC counting unrelated to clinical follow up.

Award

Patrizia Paterlini-Brechot is awarded the prestigious American society of cytopathology award for New Frontiers in Cytology.

Publication

Khoja L. et al
Melanoma Res. 2014 Feb;24(1):40-6.
Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma

Publication

Mazzini C. et al
Cancers (Basel) 2014 Feb 7;6(1):323-32.
Circulating Tumor Cells Detection and Counting in Uveal Melanomas by a Filtration-Based Method

Publication

Cummings J. et al
BMC Cancer 2014 Mar; 28;14:226.
Optimisation of an immunohistochemistry method for the determination of androgen receptor expression levels in circulating tumour cells.

Publication

Hofman V. et al
Curr Mol Med 2014 May; 14(4):440-56.
Detection of circulating tumor cells from lung cancer patients in the era of targeted therapy: promises, drawbacks and pitfalls.

Publication

Khoja et al.
Ann Oncol (2015) 26 (1): 33-39, first published online June 6, 2014
Circulating Tumor Cells As Tumor Biomarkers In Melanoma:Detection Methods And Clinical Relevance.

Publication

Morris KL. et al
Cancer Chemother Pharmacol 2014 June ; 74(2):323-32.
Circulating biomarkers in hepatocellular carcinoma.

Publication

Chinen LT. et al
Onco Targets Ther. 2014 Sep 16;7:1609-1617.
Isolation, detection, and immunomorphological characterization of circulating tumor cells (CTCs) from patients with different types of sarcoma using isolation by size of tumor cells: a window on sarcoma-cell invasion.

Publication

LeBleu VS. et al
Nat Cell Biol. 2014 Oct;16(10):992-1003.
PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis

Publication

Ilie. et all
PLOS One. 2014 Oct 31;9(10) :e111597l
« Sentinel » Circulating Tumor Cells Allow Early Diagnosis of Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease

Publication

Faugeroux et al.
Front Oncol. 2014; 4: 281, published online 2014 Nov 5
Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

Publication

Paterlini-Bréchot
Cancer Microenviron. 2014 Dec;7(3):161-76
Circulating Tumor Cells: Who is the Killer?

Publication

Ismailova et al.
J Clin Med Kaz 2015; 1(35):15-20
Detection of Circulating Tumor cells by ISET and their molecular characterization for use as liquid biopsy.

Publication

Abdallah et al.
Int J Cancer. 2015 Sep 15;137(6):1397-405. Epub 2015 Mar 11
Thymidylate synthase expression in circulating tumor cells: a new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients.

Publication

Pailler et al.
Ann Oncol. 2015 Jul;26(7):1408-15. Epub 2015 Apr 6
High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

Commercialization

ISET Blood Cytopathology available in France. (Paris)

Publication

Buim et al.
Cancer Biol Ther. 2015;16(9):1289-95. Epub 2015 Aug 7
Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer.

Publication

Hofman et al.
Cancer Cytopathol. 2016 Jun;124(6):380-7. Epub 2015 Nov 20
Detection and characterization of circulating tumor cells in lung cancer: Why and how?

Publication

Poruk et al.
Ann Surg. 2016 Jan 7. (Epub ahead of print)
Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma.

Publication

Salvianti et al.
Front Mol Biosci. 2016 Jan 8, 2:76
Tumor-Related Methylated Cell-Free DNA and Circulating Tumor Cells in Melanoma.

Publication

Hong et al.
Tumour Biol. 2016 May;37(5):5663-74. Epub 2016 Jan 13
Phenotype of circulating tumor cell: face-off between epithelial and mesenchymal masks.

Commercialization

ISET Blood Cytopathology is available in Italy. (Naples)

Publication

Long et al.
Cancer Med. 2016 Jun;5(6):1022-30. Epub 2016 Mar 6
High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

Publication

Abdallah et al.
Int J Cancer. 2016 Aug 15;139(4):890-8. Epub 2016 Apr 28
MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer.

Publication

Massard et al.
Oncotarget. 2016 Jul 4.(Epub ahead of print)
Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castrationresistant prostate cancer: a report from the PETRUS prospective study.

Publication

Pailler et al.
BMC Cancer. 2016 Jul 14;16(1):477
Method for semi-automated microscopy of filtration-enriched circulating tumor cells.

Publication

Poruk et al.
Clin Cancer Res, 2016 Oct 27, [Epubahead of print]
Circulating tumor cells expressing markers of tumor initiating cells predict poor survival and cancer recurrence in patients with pancreatic ductal adenocarcinoma

Publication

Williamnson et al.
Nat Commun. 2016 Nov 9;7:13322. doi: 10.1038/ncomms13322.
Vasculogenic mimicry in small cell lung cancer

Publication

Kallergie et al.
Cell Physiol Biochem 2016;40:411-419 doi: 10.1159/000452556
Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs).

Publication

Souza e Silva et al.
Onco Targets Ther. 2016, Dec. 9: 7503–7513. doi: https://doi.org/10.2147/OTT.S115268
Early detection of poor outcome in patients with metastatic colorectal cancer: tumor kinetics evaluated by circulating tumor cells.

Publication

Laget et al.
PLoS ONE 12(1): e0169427. doi:10.1371/journal.pone.0169427 Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion.

Publication

Ilie et al.
Oncotarget 2017 Feb 15. doi:10.18632/oncotarget.15345 [Epub ahead of print] Expression of MET in circulating tumor cells correlates with expression in tumor tissue from advanced-stage lung cancer patients.

Publication

Pailler et al.
Cancer Res 77(9) May 1, 2017. doi: 10.1158/0008-5472.CAN-16-3072 Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non–Small Cell Lung Cancer Patients

Publication

Matikas et al.
Translational Oncology 2017 June 26; 10: 693-698. Detection of KRAS Exon 2 Mutations in Circulating Tumor Cells Isolated by the ISET System from Patients with RAS Wild Type Metastatic Colorectal Cancer.

Publication

Corassa et al.
Applied Cancer Research 201737:12 Circulating tumor cells as a new and additional approach to follow-up patients with serous low-grade ovarian adenocarcinoma – a case report and review of the literature

Publication

Poruk et al.
Pancreas 2017;46: 943–947. Circulating Epithelial Cells in Intraductal Papillary Mucinous Neoplasms and Cystic Pancreatic Lesions.

Publication

Fanelli et al.
Head & Neck 2017 1:10. Evaluation of incidence, significance, and prognostic role of circulating tumor microemboli and transforming growth factor-b receptor I in head and neck cancer.

Publication

Ried et al.
Asian Pacific Journal of Cancer Prevention 2017 Aug 27; 18(8):2275-2285. Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

Publication

Ilie et al.
Annals of Oncology 2017 Oct 09; Epub Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small cell lung cancer.
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