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Michel Sadelain

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Michel Sadelain
Michel Sadelain, Genetic Engineer and Cell Therapist
Born1960
Paris, France
Alma mater
  • University of Paris
  • University of Alberta
  • Massachusetts Institute of Technology (MIT)
Known for
  • T cell engineering
  • chimeric antigen receptor (CAR) therapy
  • Globin gene therapy
Awards
Scientific career
Institutions
WebsiteThe Michel Sadelain Lab

Michel Sadelain (born 1960) is a genetic engineer and cell therapist at Memorial Sloan Kettering Cancer Center, New York, New York, where he holds the Steve and Barbara Friedman Chair.[2] 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.[2] 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.[3] Dr. Sadelain is an elected member of the National Academy of Medicine of France[4] and the American Academy of Arts & Sciences.[5]

Education and career

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Sadelain was born in 1960 in Paris, France,[6] where he earned his MD at the University of Paris, France, in 1984.[7] After obtaining his PhD 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.[7] While at MIT, Sadelain began his research on genetic engineering.[8] 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.[8] In 2008, he founded the Center for Cell Engineering at Memorial Sloan Kettering.[8] 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.[7]

Research

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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 conceptualization and design of synthetic receptors for antigen, which he named chimeric antigen receptors (CARs).[9] T cells can be engineered to express a CAR to acquire the ability to recognize and destroy cancer cells. Sadelain has referred to CAR T cells as a “living drug.”[10] A CAR typically comprises an antibody fragment (scFv) to recognize the cancer and a modular signaling domain to activate the T cell and promote T cell multiplication and persistence. CAR T cells are made by extracting a cancer patient's T cells, inserting a CAR into the cell using a vector such as a gamma-retroviral or lentiviral vector, and then re-infusing the genetically instructed T cells. Sadelain's current research makes use of genome editing, which he showed makes better CAR T cells when the CAR is expressed from the TRAC locus.[11][12][13]

Sadelain's laboratory designed second generation CARs, which are endowed with both activating and costimulatory properties, which is integral to the success of CAR therapies.[14] In 2003, Sadelain's lab identified CD19 as a target for CAR therapy in mice. 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.[15][16][17] 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.[18]

Sadelain's research on “off-the-shelf” CAR T cells derived from induced pluripotent stem cells (iPSCs) is now being developed in a collaboration with 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.[19] In 2013, Sadelain co-founded Juno Therapeutics Inc.[20][21]

Sadelain also designed lentiviral vectors encoding the β-globin gene for the treatment of severe hemoglobinopathies, which include β-thalassemia and sickle cell disease.[22] The MSK team was the first to treat patients with β-thalassemia in the US.[22] The history of the field and Sadelain's contributions are narrated in the 2021 George Stamatoyannopoulos Memorial Lecture at the annual meeting of the American Society of Gene and Cell Therapy.[23][1]

Patents

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Sadelain holds numerous patents in immunotherapy.[24] Sadelain is a named inventor on U.S. Patent No. 7446190B2 covering nucleic acids encoding chimeric T cell receptors.[25] Sadelain is also 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).[26] 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.[27][24][28]

Significant publications

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Memberships

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Awards

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References

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  1. ^ a b c "Two Memorial Sloan Kettering Experts Awarded for Pioneering Work - The ASCO Post". ascopost.com. Retrieved 2021-08-03.
  2. ^ a b "The Michel Sadelain Lab". MSKCC. Retrieved June 15, 2020.
  3. ^ "How Scientists Built a 'Living Drug' to Beat Cancer". Wired. ISSN 1059-1028. Retrieved 2020-06-15.
  4. ^ a b "Fiche membre – Michel SADELAIN". Académie nationale de médecine | Une institution dans son temps (in French). Retrieved 2024-09-13.
  5. ^ a b "2024 New Member List". American Academy of Arts and Sciences (amacad.org). Retrieved 2024-09-13.
  6. ^ "La Fondation ARC félicite le chercheur français Michel Sadelain, nouveau lauréat du prestigieux Breakthrough Prize en Life Science". Fondation ARC de la recherche sur le cancer (in French). 2023-10-24. Retrieved 2024-04-14.
  7. ^ a b c d e f g "Michel Sadelain, M.D., Ph.D." Cancer Research Institute. Retrieved 2020-07-15.
  8. ^ a b c "Prominent Immunotherapy Researcher Sees Success Beyond the Challenges - The ASCO Post". www.ascopost.com. Retrieved 2020-07-15.
  9. ^ 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.
  10. ^ Grady, Denise (2013-03-20). "Cell Therapy Shows Promise for Acute Type of Leukemia". The New York Times. ISSN 0362-4331. Retrieved 2023-09-13.
  11. ^ 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.
  12. ^ "'Living Drug' That Fights Cancer By Harnessing Immune System Clears Key Hurdle". www.wbur.org. Retrieved 2020-09-03.
  13. ^ "Inside Cancer's Newest Miracle Cure". Time. Retrieved 2020-09-03.
  14. ^ 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.
  15. ^ "The Possibilities and Risks of Genetically Altering Immune Cells to Fight Cancer". Smithsonian Magazine. Retrieved 2020-09-03.
  16. ^ 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.
  17. ^ "Cell Therapy Shows Remarkable Ability to Eradicate Cancer in Clinical Study". www.mskcc.org. 2014-02-19. Retrieved 2020-09-03.
  18. ^ 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.
  19. ^ "Preliminary Results Show Activity for Mesothelin‑Directed CAR T-Cell Therapy in Malignant Mesothelioma - The ASCO Post". ascopost.com. Retrieved 2020-09-03.
  20. ^ "Biotech's Coming Cancer Cure". MIT Technology Review. Retrieved 2020-09-03.
  21. ^ "Letter Agreement, Memorial Sloan Kettering Cancer Center". www.sec.gov. Retrieved 2020-09-03.
  22. ^ a b 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.
  23. ^ "2021 ASGCT George Stamatoyannopoulos Memorial Lecture | Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 2021-08-03.
  24. ^ a b "Michel Sadelain Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved 2020-07-15.
  25. ^ "Analytics for US Patent No. 8399645, Chimeric receptors with 4-1BB stimulatory signaling domain". www.patentbuddy.com. Retrieved 2021-08-03.
  26. ^ "Fate Therapeutics, MSK to Develop Off-the-Shelf T-Cell Immunotherapies". GEN - Genetic Engineering and Biotechnology News. 2016-09-07. Retrieved 2020-07-15.
  27. ^ "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.
  28. ^ "Patent Database Search Results: "michel sadelain" in US Patent Collection". patft.uspto.gov. Retrieved 2020-07-15.
  29. ^ "CRI Clinical Accelerator Leadership". Cancer Research Institute. Retrieved 2020-07-15.
  30. ^ 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.
  31. ^ "William B. Coley Award". Cancer Research Institute. Retrieved 2020-07-15.
  32. ^ "Michel Sadelain recognized for Thalassemia work". stemcell.ny.gov. NYSTEM.
  33. ^ "Award". The Passano Foundation, Inc. Retrieved 2020-07-15.
  34. ^ "World-Renowned Immunologist Michel Sadelain Wins Pasteur-Weizmann/Servier Prize". Memorial Sloan Kettering Cancer Center. 2018-10-16. Retrieved 2020-07-15.
  35. ^ "Gabbay award given to scientists whose research brought about new cancer treatments". BrandeisNOW. Retrieved 2020-07-15.
  36. ^ "Michel Sadelain, 2019 International Prize". Inserm - From science to health. Retrieved 2020-09-03.
  37. ^ "The Golden Age of Gene Therapy: Past, Present and Future Perspectives". BigMarker.com. Retrieved 2020-09-03.
  38. ^ "Citation Laureates 2023_Physiology or Medicine". Citation Laureates. Clarivate. Archived from the original on September 19, 2023. Retrieved September 19, 2023.
  39. ^ "Breakthrough Prize Announces 2024 Laureates in Life Sciences, Fundamental Physics, and Mathematics". BREAKTHROUGH PRIZE. September 14, 2023. Retrieved September 14, 2023.
  40. ^ Canada Gairdner International Award 2024
  41. ^ "2024 Warren Alpert Foundation Prize awardees Announced". Warren Alpert Foundation (warrenalpert.org). Retrieved 2024-09-13.
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