Michel Sadelain

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Michel Sadelain, MD, PhD
Immunologist Michel Sadelain.jpg
Michel Sadelain, Genetic Engineer and Cell Therapist
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
  • Globin gene therapy
Awards
Scientific career
Institutions
Website The Michel Sadelain Lab

Michel Sadelain is an 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]

Contents

Education and career

Sadelain was born in France, where he earned his MD at the University of Paris, France, in 1984. [4] 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. [4] While at MIT, Sadelain began his research on genetic engineering. [5] 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. [5] In 2008, he founded the Center for Cell Engineering at Memorial Sloan Kettering. [5] 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. [4]

Research

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). [6] 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.” [7] 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. [8] [9] [10]

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. [11] 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. [12] [13] [14] 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. [15]

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. [16] In 2013, Sadelain co-founded Juno Therapeutics Inc. [17] [18]

Sadelain also designed lentiviral vectors encoding the β-globin gene for the treatment of severe hemoglobinopathies, which include β-thalassemia and sickle cell disease. [19] The MSK team was the first to treat patients with β-thalassemia in the US. [19] 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. [20] [21]

Patents

Sadelain holds numerous patents in immunotherapy. [22] Sadelain is a named inventor on U.S. Patent No. 7446190B2 covering nucleic acids encoding chimeric T cell receptors. [23] 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). [24] 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. [25] [22] [26]

Significant publications

Memberships

Awards

Related Research Articles

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In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.

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<span class="mw-page-title-main">B-cell maturation antigen</span> Protein-coding gene in the species Homo sapiens

B-cell maturation antigen, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.

Blinatumomab, sold under the brand name Blincyto, and known informally as blina, is a biopharmaceutical medication used as a second-line treatment for Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia. It belongs to a class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells. In December 2014, it was approved by the US Food and Drug Administration under the accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at the time of approval. Blinatumomab is given via intravenous infusion.

Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.

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References

  1. ↑ "Two Memorial Sloan Kettering Experts Awarded for Pioneering Work - The ASCO Post". ascopost.com. Retrieved 2021-08-03.
  2. 1 2 "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. 1 2 3 4 5 6 7 "Michel Sadelain, M.D., Ph.D." Cancer Research Institute. Retrieved 2020-07-15.
  5. 1 2 3 "Prominent Immunotherapy Researcher Sees Success Beyond the Challenges - The ASCO Post". www.ascopost.com. Retrieved 2020-07-15.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ "'Living Drug' That Fights Cancer By Harnessing Immune System Clears Key Hurdle". www.wbur.org. Retrieved 2020-09-03.
  10. ↑ "Inside Cancer's Newest Miracle Cure". Time. Retrieved 2020-09-03.
  11. ↑ 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.
  12. ↑ "The Possibilities and Risks of Genetically Altering Immune Cells to Fight Cancer". Smithsonian Magazine. Retrieved 2020-09-03.
  13. ↑ 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.
  14. ↑ "Cell Therapy Shows Remarkable Ability to Eradicate Cancer in Clinical Study". www.mskcc.org. 2014-02-19. Retrieved 2020-09-03.
  15. ↑ 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.
  16. ↑ "Preliminary Results Show Activity for Mesothelin‑Directed CAR T-Cell Therapy in Malignant Mesothelioma - The ASCO Post". ascopost.com. Retrieved 2020-09-03.
  17. ↑ "Biotech's Coming Cancer Cure". MIT Technology Review. Retrieved 2020-09-03.
  18. ↑ "Letter Agreement, Memorial Sloan Kettering Cancer Center". www.sec.gov. Retrieved 2020-09-03.
  19. 1 2 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.
  20. ↑ "2021 ASGCT George Stamatoyannopoulos Memorial Lecture | Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 2021-08-03.
  21. ↑ "Two Memorial Sloan Kettering Experts Awarded for Pioneering Work - The ASCO Post". ascopost.com. Retrieved 2021-08-03.
  22. 1 2 "Michel Sadelain Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved 2020-07-15.
  23. ↑ "Analytics for US Patent No. 8399645, Chimeric receptors with 4-1BB stimulatory signaling domain". www.patentbuddy.com. Retrieved 2021-08-03.
  24. ↑ "Fate Therapeutics, MSK to Develop Off-the-Shelf T-Cell Immunotherapies". GEN - Genetic Engineering and Biotechnology News. 2016-09-07. Retrieved 2020-07-15.
  25. ↑ "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.
  26. ↑ "Patent Database Search Results: "michel sadelain" in US Patent Collection". patft.uspto.gov. Retrieved 2020-07-15.
  27. ↑ "CRI Clinical Accelerator Leadership". Cancer Research Institute. Retrieved 2020-07-15.
  28. ↑ 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.
  29. ↑ "William B. Coley Award". Cancer Research Institute. Retrieved 2020-07-15.
  30. ↑ "Michel Sadelain recognized for Thalassemia work". stemcell.ny.gov. NYSTEM.
  31. ↑ "Award". The Passano Foundation, Inc. Retrieved 2020-07-15.
  32. ↑ "World-Renowned Immunologist Michel Sadelain Wins Pasteur-Weizmann/Servier Prize". Memorial Sloan Kettering Cancer Center. 2018-10-16. Retrieved 2020-07-15.
  33. ↑ "Gabbay award given to scientists whose research brought about new cancer treatments". BrandeisNOW. Retrieved 2020-07-15.
  34. ↑ "Michel Sadelain, 2019 International Prize". Inserm - From science to health. Retrieved 2020-09-03.
  35. ↑ "The Golden Age of Gene Therapy: Past, Present and Future Perspectives". BigMarker.com. Retrieved 2020-09-03.
  36. ↑ "Two Memorial Sloan Kettering Experts Awarded for Pioneering Work - The ASCO Post". ascopost.com. Retrieved 2021-08-03.
  37. ↑ "Citation Laureates 2023_Physiology or Medicine". Citation Laureates. Clarivate. Archived from the original on September 19, 2023. Retrieved September 19, 2023.
  38. ↑ "BREAKTHROUGH PRIZE ANNOUNCES 2024 LAUREATES IN LIFE SCIENCES, FUNDAMENTAL PHYSICS, AND MATHEMATICS". BREAKTHROUGH PRIZE. September 14, 2023. Retrieved September 14, 2023.
  39. ↑ Canada Gairdner International Award 2024
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