Michel Sadelain, MD, PhD

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Overview

Sadelain is a globally recognized pioneer of chimeric antigen receptor T cell (CAR-T) immunotherapy, a groundbreaking approach to cancer treatment. CAR-T therapy uses genetic engineering on a sample of a patient’s own T cells to transform them into “living drugs” for the treatment of their disease.

Sadelain led the development of CAR-T cells targeting CD19 —unique markers found on the surface of blood cancer cells—and established genetic engineering and cell manufacturing capabilities to translate this research. This critical groundwork enabled Sadelain and his team to start treating patients with refractory leukemias in 2007.

In 2017, the FDA approved the first CAR-T therapies — the first genetically engineered cell therapy of any kind — for childhood acute lymphoblastic leukemia and certain lymphomas. This ushered in a new class of drugs based on T cell engineering. Since then, CAR-T therapies have been approved for additional types of lymphoma and to multiple myeloma.

Sadelain and his team are continuing to explore ways to make CAR-T therapies safer, more effective, and broaden their use to different types of cancers. Sadelain’s lab will also investigate how CAR-T engineering could be used to treat a diverse array of diseases and conditions beyond cancer, as well as sustainable means to make cell therapies more accessible.

Sadelain joined Columbia University from Memorial Sloan Kettering, where he was the Stephen and Barbara Friedman Chair and director of the Center for Cell Engineering. Sadelain completed his MD at University of Paris; conducted his PhD research at the University of Alberta; and worked as a postdoctoral fellow at the Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology.

Sadelain has been elected to the American Society for Clinical Investigation, American Association for Cancer Research, American Society for Clinical Investigation, American Society of Gene and Cell Therapy, American Academy of Arts and Sciences, and the National Academy of Medicine of France.

Sadelain has won the Breakthrough Prize for Life Sciences, Canada Gairdner International Award, Warren Alpert Foundation Prize, American Society of Gene and Cell Therapy Outstanding Achievement Award, Leopold Griffuel Award, INSERM International Prize, Jacob and Louise Gabbay Award in Biotechnology and Medicine, Passano Laureate, Pasteur Weizmann/Servier Prize at the Academy of Sciences in Paris, Cancer Research Institute Coley award, and more.

Administrative Titles

  • Director of the Columbia Initiative in Cell Engineering and Therapy (CICET)
  • Director of the Cancer Cell Therapy Initiative in the Herbert Irving Comprehensive Cancer Center (HICCC)

Credentials & Experience

Education & Training

  • MD, 1984 University of Paris, France
  • PhD, 1989 University of Alberta, Canada
  • Fellowship: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology

Committees, Societies, Councils

  • CRI Accelerator Leadership
  • The American Society for Clinical Investigation
  • American Association for Cancer Research (AACR)
  • American Society for Clinical Investigation (ASCI)
  • American Society of Gene and Cell Therapy (ASGCT)
  • American Society of Hematology (ASH)
  • American Academy of Arts & Sciences
  • National Academy of Medicine of France

Honors & Awards

  • Warren Alpert Foundation Prize, Harvard University (2024)
  • Canada Gairdner International Award (2024)
  • Breakthrough Prize (2023)
  • Clarivate Citation Laureate (2023)
  • American Society of Gene & Cell Therapy Outstanding Achievement Award (2021)
  • ASGCT Outstanding Achievement Award (2021)
  • Leopold Griffuel Award (2020)
  • INSERM International Prize (2019)
  • Jacob and Louise Gabbay Award in Biotechnology and Medicine (2019)
  • Passano Laureate and Physician Scientist Award, Johns Hopkins University (2018)
  • Pasteur Weizmann/Servier Prize at the Academy of Sciences in Paris (2018)
  • Inventor of the Year Award, New York Intellectual Property Law Association (NYIPLA) (2014)
  • Antonio Cao Award for Research in Thalassemia or Hemoglobinopathies, Palermo, Italy (2013)
  • Sultan Bin Khalifa International Thalassemia Award (2013)
  • Coley Award of the Cancer Research Institute for Distinguished Research in Tumor Immunology (2012)

Research

Selected Publications

  1. Jain N, Zhao Z, Koche RP, Antelope C, Gozlan Y, Montalbano A, Brocks D, Lopez M, Dobrin A, Shi Y, Gunset G, Giavridis T, Sadelain M. Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T cell function. Cancer Discovery. 2023
  2. Haubner S, Mansilla-Soto J, Nataraj S, Kogel F, Chang Q, de Stanchina E, Lopez M, Ng MR, Fraser K, Subklewe M, Park JH, Wang X, Rivière I, Sadelain M. Cooperative CAR targeting to selectively eliminate AML and minimize escape. Cancer Cell. 2023 Oct 4:S1535-6108(23)00326-4.
  3. Zhao Z, Sadelain M. CAR T cell design: approaching the elusive AND-gate. Cell Res. 2023 Oct;33(10):739-740.
  4. Hamieh M, Mansilla-Soto J, Rivière I, Sadelain M. Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating. Cancer Discov. 2023 Apr 3;13(4):829-843.
  5. Jain N, Zhao Z, Feucht J, Koche R, Iyer A, Dobrin A, Mansilla-Soto J, Yang J, Zhan Y, Lopez M, Gunset G, Sadelain M. TET2 guards against unchecked BATF3-induced CAR T cell expansion. Nature. 2023 Mar;615(7951):315-322.
  6. Odak A, Yuan H, Feucht J, Cantu VA, Mansilla-Soto J, Friederike Kogel F, Eyquem J, Everett J, Bushman FD, Leslie CS, Sadelain M. Novel extragenic genomic safe harbors for precise therapeutic T-cell engineering. Blood. 2023 Jun 1;141(22):2698-2712. [PMID: 36745870]
  7. He C, Mansilla-Soto J, Khanra N, Hamieh M, Bustos V, Paquette AJ, Garcia Angus A, Shore DM, Rice WJ, Khelashvili G, Sadelain M, Meyerson JR. CD19 CAR antigen engagement mechanisms and affinity tuning. Sci Immunol. 2023 Mar 10;8(81):eadf1426. [PMID: 36867678]
  8. Hamieh M, Mansilla-Soto J, Rivière I, Sadelain M. Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating. Cancer Discov. 2023 Mar 24;OF1-OF15. [PMID: 36961206]
  9. Jain N, Zhao Z, Feucht J, Koche R, Iyer A, Dobrin A, Mansilla-Soto J, Yang J, Zhan Y, Lopez M, Gunset G, Sadelain M. TET2 guards against unchecked BATF3-induced CAR T cell expansion. Nature. 2023 Mar;615(7951):315-322. [PMID: 36755094]
  10. Odak A, Yuan H, Feucht J, Cantu VA, Mansilla-Soto J, Kogel F, Eyquem J, Everett JK, Bushman FD, Leslie C, Sadelain M. Novel extragenic genomic safe harbors for precise therapeutic T cell engineering. Blood. 2023 Feb 6:blood. [PMID: 36745870]
  11. van der Stegen SJC, Lindenbergh PL, Petrovic RM, Xie H, Diop MP, Alexeeva V, Shi Y, Mansilla-Soto J, Hamieh M, Eyquem J, Cabriolu A, Wang X, Abujarour R, Lee T, Clarke R, Valamehr B, Themeli M, Riviere I, Sadelain M. Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells. Nat Biomed Eng. 2022 Aug 8 [PMID: 35941192]
  12. Cabriolu A, Odak A, Zamparo L, Yuan H, Leslie CS, and Michel Sadelain. Globin vector regulatory elements are active in early hematopoietic progenitor cells. Molecular Therapy. March 2, 2022. [PMID: 35247584]
  13. Mansilla-Soto J, Eyquem J, Haubner S, Hamieh M, Feucht J, Paillon N, Zucchetti AE, Li Z, Sjöstrand M, Lindenbergh PL, Saetersmoen M, Dobrin A, Maurin M, Iyer A, Garcia Angus A, Miele MM, Zhao Z, Giavridis T, van der Stegen SJC, Tamzalit F, Rivière I, Huse M, Hendrickson RC, Hivroz C, and Sadelain M. HLA-independent T cell receptors for targeting tumors with low antigen density. Nature Medicine. January 13, 2022. [PMID: 35027758]
  14. Boulad F, Maggio A, Wang X, Moi P, Acuto S, Kogel F, Takpradit C, Prockop S, Mansilla-Soto J, Cabriolu?A, Odak A, Qu J, Thummar K, Du F, Shen L, Raso S, Barone R, Di Maggio R, Pitrolo L, Giambona A, Mingoia M, Everett JK, Hokama P, Roche AM, Cantu VA, Adhikari H, Reddy S, Bouhassira E, Mohandas N, Bushman FD, Rivière I and Sadelain M. Lentiviral globin gene therapy with reduced-intensity conditioning in adults with β-thalassemia: a phase 1 trial. Nature Medicine. January 3, 2022. [PMID: 34980909]
  15. Amor, C., Feucht, J., Leibold, J. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature. 2020 Jul;583(7814):127-132. [PMID: 32555459]
  16. Hamieh M, Dobrin A, Cabriolu A, van der Stegen SJC, Giavridis T, Mansilla-Soto J, Eyquem J, Zhao Z, Whitlock BM, Miele MM, Li Z, Cunanan KM, Huse M, Hendrickson RC, Wang X, Rivière I, Sadelain M. CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature. 2019 Apr;568(7750):112-116. [PMID: 30918399]
  17. Mestermann K, Giavridis T, Weber J, Rydzek J, Frenz S, Nerreter T, Andreas M, Sadelain M, Einsele H, Hudecek M. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Sci. Transl. Med. 11, eaau5907 (2019). [PMID: 31270272]
  18. Feucht, F., Sun, J., Eyquem, J., Ho, Y., Zhao, Z., Leibold, J., Dobrin, A., Cabriolu, A., Hamieh, M., Sadelain, M. Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nature Medicine Dec 17, 2018.
  19. June CH, Sadelain M. Chimeric Antigen Receptor Therapy. N Engl J Med. 2018 Jul 5;379(1):64-73.
  20. Giavridis T., van der Stegen S.J.C., Eyquem J., Hamieh M., Piersigilli A., Sadelain M. CAR T cell–induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nature Medicine. Online 28 May 2018. DOI: 10.1038/s41591-018-0041-7.
  21. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, Roshal M, Maslak P, Davila M, Brentjens RJ, Sadelain M. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):449-459.
  22. Sadelain M, Rivière I, Riddell S. Therapeutic T cell engineering. Nature. 2017 May 24;545(7655):423-431.
  23. Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M, Cunanan KM, Odak A, Gönen M, Sadelain M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017 Mar 2;543(7643):113-117.
  24. Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells. Zhao Z, Condomines M, van der Stegen SJ, Perna F, Kloss CC, Gunset G, Plotkin J, Sadelain M. Cancer Cell. 2015 Oct 12;28(4):415-28.
  25. Adusumilli PS, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, Jones DR, Sadelain M. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014 Nov 5;6(261):261ra151. doi: 10.1126/scitranslmed.3010162.
  26. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SC, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He W, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DCG, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R. Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci Transl Med 19 February 2014. Vol. 6, Issue 224, p. 224ra25. DOI: 10.1126/scitranslmed.3008226.
  27. Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses. Sci Transl Med. 2013 Dec 11;5(215):215ra172. doi: 10.1126/scitranslmed.3006597.
  28. Themeli M, Kloss C, Ciriello G, Fedorov VD, Perna F, Gonen M, Sadelain M. Generation of functional tumor-targeted T lymphocytes from human chimeric antigen receptor-engineered induced pluripotent stem cells. Nat Biotech. 2013 Aug 11.doi: 10.1038/nbt.2678. [Epub ahead of print].
  29. Brentjens RJ, Davila ML, Riviere I, Park J. et al. CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia. Sci Transl Med. 2013 Mar 20;5(177):177ra38. [PMID: 23515080]
  30. Brentjens RJ, Latouche JB, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med. 2003 Mar;9(3):279-86. [PMID: 12579196]
  31. Maher J, Brentjens RJ, Gunset G, Rivière I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol. 2002 Jan;20(1):70-5. [PMID: 11753365]
  32. May C, Rivella S, Callegari J, Heller G, Gaensler KM, Luzzatto L, Sadelain M. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature. 2000 Jul 6;406(6791):82-6.
  33. Krause A, Guo HF, Latouche JB, Tan C, Cheung NK, Sadelain M. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med. 1998 Aug 17;188(4):619-26.