Michel Sadelain

Michel Sadelain is a physician-scientist at Memorial Sloan Kettering Cancer Center, New York, New York, where he holds the Steve and Barbara Friedman Chair.[1] He is the founding director of the Center for Cell Engineering and the head of the Gene Transfer and Gene Expression Laboratory. He is a member of the department of medicine at Memorial Hospital and of the immunology program at the Sloan Kettering Institute.[1] He is best known for his major contributions to T cell engineering and chimeric antigen receptor (CAR) therapy, an immunotherapy based on the genetic engineering of a patient's own T cells to treat cancer.[2]

Michel Sadelain, M.D., Ph.D.
Immunologist Michel Sadelain
Born
France
Alma mater
  • University of Paris
  • University of Alberta
  • Massachusetts Institute of Technology (MIT)
Known for
  • T cell engineering
  • chimeric antigen receptor (CAR) therapy
Awards
  • 2019 Jacob and Louise Gabbay Award in Biotechnology and Medicine
  • 2019 INSERM International Prize
  • 2020 Leopold Griffuel Award
Scientific career
Institutions
WebsiteThe Michel Sadelain Lab

Education and Career

Sadelain was born in France, where he earned his M.D. at the University of Paris, France, in 1984.[3] After obtaining his Ph.D. in immunology at the University of Alberta in Edmonton, Canada, in 1989, he trained as a postdoctoral fellow at the Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts.[3] While at MIT, Sadelain began his research on genetic engineering.[4] In 1994, Sadelain joined Memorial Sloan Kettering as an assistant member in the Sloan Kettering Institute, where he established programs on human hematopoietic stem cell and T cell engineering.[4] In 2008, at the bequest of then-Memorial Sloan Kettering President Harold Varmus and Sloan Kettering Institute Director Thomas Kelly, he founded the Center for Cell Engineering at Memorial Sloan Kettering.[4] He is a past president of the American Society of Cell and Gene Therapy (2014–2015) and previously served on its board of directors from 2004 to 2007. He served as a member of the Recombinant DNA Advisory Committee (RAC) of the NIH from 2013 to 2015.[3]

Research

In his lab at the Sloan Kettering Institute, Sadelain and his team study gene transfer in hematopoietic stem cells and T cells, the regulation of transgene expression, the biology of chimeric antigen receptors, and therapeutic strategies to enhance immunity against cancer.

Sadelain is a recognized leader in the concept and design of synthetic receptors for antigen, which he named chimeric antigen receptors and classified into first and second generation.[5] The design of second generation CARs, which are endowed with both activating and costimulatory properties, REF Maher is integral to the success of CAR therapies.[6] In 2003, Sadelain's lab identified CD19 as an effective target for CAR therapy in mice.[7] Following the establishment of clinical CAR T cell manufacturing by Dr. Isabelle Rivière at MSK, Sadelain's team was the first to report on molecular complete responses induced by CD19 CAR T cells in adults with relapsed, refractory acute lymphoblastic leukemia.[8][9][10] The MSK team received FDA breakthrough designation for this treatment in 2014. The US FDA approved the first CAR therapies, targeting CD19 with second generations CARs, in 2017.[11]

Sadelain also devised how to design lentivciral vectors encoding the ß-globin gene for the treatment of severe hemoglobinopathies, which included ß-thalassemia and sickle cell disease.[12] The MSK team was the first to treat patients with ß-thalassemia in the US.[13]

Sadelain's ongoing research at MSK and SKI continues to explore “synthetic immunity,”, further improving the design, development, and clinical translation of cell-based immunotherapies. CAR T cells have become known as “living drugs,” a term he coined to describe immune cells genetically endowed with supraphysiological properties.[14][15] Sadelain's current research makes large ample use of genome editing, which he showed enhances CAR T cells when the CAR is expressed from the TRAC locus.[16]

Sadelain's research on “off-the-shelf” CAR T cells derived from induced pluripotent stem cells (iPSCs) is now being developed by Fate Therapeutics. His research with Dr. Prasad S. Adusumilli led to a collaboration with Atara Biotherapeutics, Inc. for a product candidate to treat malignant mesothelioma using mesothelin-targeted CAR T cells named icasM28z.[17] In 2013, Sadelain co-founded Juno Therapeutics Inc.[18][19]

Patents

Sadelain holds 13 patents in immunotherapy.[20] Sadelain is named on patent U.S. Patent No. 10,370,452 covering compositions and uses of effector T cells expressing a chimeric antigen receptor (CAR), where such T cells are derived from a pluripotent stem cell including an induced pluripotent stem cell (iPSC).[21] The patent is licensed for off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell product candidate known as FT819.[22][20][23]

Significant Publications

Memberships
  • CRI Accelerator Leadership[24]
  • The American Society for Clinical Investigation[3]
  • American Association for Cancer Research (AACR)[25]
  • American Society for Clinical Investigation (ASCI)[3]
  • American Society of Gene and Cell Therapy (ASGCT)[3]
  • American Society of Hematology (ASH)[3]

Awards
  • 2012 William B. Coley Award.[26]
  • 2013 Sultan Bin Khalifa International Thalassemia Award[27]
  • 2017 Passano Laureate and Physician Scientist Award[28]
  • 2018 Pasteur-Servier-Weizmann Prize Laureate.[29]
  • 2019 Jacob and Louise Gabbay Award in Biotechnology and Medicine[30]
  • 2019 INSERM International Prize[31]
  • 2020 Leopold Griffuel Award[32]

References
  1. "The Michel Sadelain Lab". MSKCC. Retrieved June 15, 2020.
  2. "How Scientists Built a 'Living Drug' to Beat Cancer". Wired. ISSN 1059-1028. Retrieved 2020-06-15.
  3. "Michel Sadelain, M.D., Ph.D." Cancer Research Institute. Retrieved 2020-07-15.
  4. "Prominent Immunotherapy Researcher Sees Success Beyond the Challenges - The ASCO Post". www.ascopost.com. Retrieved 2020-07-15.
  5. Sadelain, Michel; Brentjens, Renier; Rivière, Isabelle (April 2009). "The promise and potential pitfalls of chimeric antigen receptors". Current Opinion in Immunology. 21 (2): 215–223. doi:10.1016/j.coi.2009.02.009. ISSN 1879-0372. PMC 5548385. PMID 19327974.
  6. Maher, John; Brentjens, Renier J.; Gunset, Gertrude; Rivière, Isabelle; Sadelain, Michel (January 2002). "Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor". Nature Biotechnology. 20 (1): 70–75. doi:10.1038/nbt0102-70. ISSN 1087-0156. PMID 11753365. S2CID 20302096.
  7. Brentjens, Renier J.; Latouche, Jean-Baptiste; Santos, Elmer; Marti, Francesc; Gong, Michael C.; Lyddane, Clay; King, Philip D.; Larson, Steven; Weiss, Mark; Rivière, Isabelle; Sadelain, Michel (March 2003). "Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15". Nature Medicine. 9 (3): 279–286. doi:10.1038/nm827. ISSN 1078-8956. PMID 12579196. S2CID 3746856.
  8. "The Possibilities and Risks of Genetically Altering Immune Cells to Fight Cancer". Smithsonian Magazine. Retrieved 2020-09-03.
  9. Brentjens, Renier J.; Davila, Marco L.; Riviere, Isabelle; Park, Jae; Wang, Xiuyan; Cowell, Lindsay G.; Bartido, Shirley; Stefanski, Jolanta; Taylor, Clare; Olszewska, Malgorzata; Borquez-Ojeda, Oriana (2013-03-20). "CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia". Science Translational Medicine. 5 (177): 177ra38. doi:10.1126/scitranslmed.3005930. ISSN 1946-6234. PMC 3742551. PMID 23515080.
  10. "Cell Therapy Shows Remarkable Ability to Eradicate Cancer in Clinical Study". www.mskcc.org. 2014-02-19. Retrieved 2020-09-03.
  11. Sadelain, Michel (2017-12-14). "CD19 CAR T Cells". Cell. 171 (7): 1471. doi:10.1016/j.cell.2017.12.002. ISSN 0092-8674. PMID 29245005. S2CID 43075053.
  12. May, Chad; Rivella, Stefano; Callegari, John; Heller, Glenn; Gaensler, Karen M. L.; Luzzatto, Lucio; Sadelain, Michel (July 2000). "Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin". Nature. 406 (6791): 82–86. Bibcode:2000Natur.406...82M. doi:10.1038/35017565. ISSN 1476-4687. PMID 10894546. S2CID 4355996.
  13. May, Chad; Rivella, Stefano; Callegari, John; Heller, Glenn; Gaensler, Karen M. L.; Luzzatto, Lucio; Sadelain, Michel (July 2000). "Therapeutic haemoglobin synthesis in β-thalassaemic mice expressing lentivirus-encoded human β-globin". Nature. 406 (6791): 82–86. Bibcode:2000Natur.406...82M. doi:10.1038/35017565. ISSN 1476-4687. PMID 10894546. S2CID 4355996.
  14. "'Living Drug' That Fights Cancer By Harnessing Immune System Clears Key Hurdle". www.wbur.org. Retrieved 2020-09-03.
  15. "Inside Cancer's Newest Miracle Cure". Time. Retrieved 2020-09-03.
  16. Eyquem, Justin; Mansilla-Soto, Jorge; Giavridis, Theodoros; van der Stegen, Sjoukje J. C.; Hamieh, Mohamad; Cunanan, Kristen M.; Odak, Ashlesha; Gönen, Mithat; Sadelain, Michel (March 2017). "Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection". Nature. 543 (7643): 113–117. Bibcode:2017Natur.543..113E. doi:10.1038/nature21405. ISSN 1476-4687. PMC 5558614. PMID 28225754.
  17. "Preliminary Results Show Activity for Mesothelin‑Directed CAR T-Cell Therapy in Malignant Mesothelioma - The ASCO Post". ascopost.com. Retrieved 2020-09-03.
  18. "Biotech's Coming Cancer Cure". MIT Technology Review. Retrieved 2020-09-03.
  19. "Letter Agreement, Memorial Sloan Kettering Cancer Center". www.sec.gov. Retrieved 2020-09-03.
  20. "Michel Sadelain Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved 2020-07-15.
  21. "Fate Therapeutics, MSK to Develop Off-the-Shelf T-Cell Immunotherapies". GEN - Genetic Engineering and Biotechnology News. 2016-09-07. Retrieved 2020-07-15.
  22. "Fate Therapeutics Announces Issuance of Foundational U.S. Patent Covering iPSC-derived CAR T Cells | Fate Therapeutics, Inc". ir.fatetherapeutics.com. Retrieved 2020-07-15.
  23. "Patent Database Search Results: "michel sadelain" in US Patent Collection". patft.uspto.gov. Retrieved 2020-07-15.
  24. "CRI Clinical Accelerator Leadership". Cancer Research Institute. Retrieved 2020-07-15.
  25. Research, American Association for Cancer (2013-04-18). "Driving Ahead with CAR T Cells". Cancer Discovery. 3 (6): 595.2–596. doi:10.1158/2159-8290.CD-NB2013-059. ISSN 2159-8274.
  26. "William B. Coley Award". Cancer Research Institute. Retrieved 2020-07-15.
  27. "Michel Sadelain recognized for Thalassemia work". stemcell.ny.gov. NYSTEM.
  28. "Award". The Passano Foundation, Inc. Retrieved 2020-07-15.
  29. "World-Renowned Immunologist Michel Sadelain Wins Pasteur-Weizmann/Servier Prize". Memorial Sloan Kettering Cancer Center. 2018-10-16. Retrieved 2020-07-15.
  30. "Gabbay award given to scientists whose research brought about new cancer treatments". BrandeisNOW. Retrieved 2020-07-15.
  31. "Michel Sadelain, 2019 International Prize". Inserm - From science to health. Retrieved 2020-09-03.
  32. "The Golden Age of Gene Therapy: Past, Present and Future Perspectives". BigMarker.com. Retrieved 2020-09-03.
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