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Charles L. Sentman, PhD

Professor of Microbiology and Immunology

Additional Titles/Positions/Affiliations
Director, Center for Synthetic Immunity

Microbiology and Immunology

University of Texas Southwestern Medical Center, Ph.D. 1990
University of Illinois, B.S., 1985

Dr. Sentman did postdoctoral training at Washington University Medical School in St. Louis, MO on the role of cell death in T cell development. From 1992 to 1995, he conducted postdoctoral research at the Microbiology and Tumor Biology Center at the Karolinska Institute in Stockholm, Sweden on natural killer (NK) cell recognition mechanisms. In 1995 he joined the medical faculty and became an investigator at the Umea Center for Molecular Pathogenesis at Umea University, Umea, Sweden where he continued his research program on NK cell receptors. In 1997, Dr. Sentman received a docentur in molecular immunology from Umea University. From 1998 to 2001, Dr. Sentman worked as a team leader and section leader at AstraZeneca R&D in Lund, Sweden with the aim to develop new pharmaceuticals against respiratory and inflammation diseases, including asthma and rheumatoid arthritis. In 2001, Dr. Sentman joined the faculty of the department of Microbiology and Immunology at Dartmouth Medical School as an assistant professor.

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Contact Information

Dartmouth Medical School
Borwell Research Building - HB 7556
1 Medical Center Drive
Lebanon NH 03756

Phone: 603-653-0611
Fax: 603-650-6223
Email: Charles.L.Sentman@Dartmouth.Edu

Professional Interests

Natural killer (NK) cells are an important part of the innate immune system and have the ability to kill tumor cells and some virus-infected cells while sparing nearby normal cells. Dr. Sentman's research interests are NK cell recognition mechanisms, the role of NK cells as a part of the immune defense against cancer and infection, and how NK cell and T cell effector mechanisms affect the tumor microenvironment. His laboratory is focused on the development of novel immunotherapy strategies for cancer, and there are several major areas of research: chimeric NK cell receptor based immunotherapy, bi-specific antibody targeting of tumors using NK cell receptors, and development of novel signaling platforms for cell based therapies.

NK receptor based chimeric antigen receptors (CARs) as immunotherapy: NK cells express a number of different receptors that can recognize tumor cells, and their ligands are expressed on many different types of tumor cells making them good targets for the treatment of cancer. Dr. Sentman’s lab has developed a novel immunotherapy targeting strategy using chimeric NKG2D receptors. These NKG2D CARs are formed by a fusion of NKG2D with a cytoplasmic signaling domain of CD3zeta. However, because NKG2D is a type II protein, the orientation of CD3zeta is reversed. NKG2D recognizes several ligands that are often expressed on tumor cells but not normal tissues. Almost 90% of human cancers are of tumor types that have been shown to express ligands for NKG2D. In addition, immunosuppressive cells (MDSCs, Tregs) may also express NKG2D ligands within the tumor microenvironment. When expressed in T cells by viral transduction, these NKG2D CARs are able to recognize tumor cells in an MHC independent manner, and they trigger T cells to produce proinflammatory cytokines and kill tumor cells upon recognition of their ligands. In fact, extensive analysis in syngeneic lymphoma and ovarian cancer models has shown that both cytotoxicity and cytokines are an essential part of the CAR T cell efficacy. Dr. Sentman’s laboratory is using this approach to target ovarian cancer, lymphoma, and myeloma, and this approach has the potential to be applied to other tumors such as breast cancer, melanoma, and osteosarcoma. His laboratory is working on development and analysis of a number of other CARs based on NK cell receptors and their ligands.

Bi-specific T cell engagers: It is possible to target tumors effectively using bi-specific antibodies that trigger T cell effector function when they also bind to ligand expressing tumor cells. Dr. Sentman’s laboratory has developed a bi-specific T cell engager or BiTE based on the scFv from anti-CD3 and NKG2D. This hybrid molecule binds to T cells via CD3 and to tumor cells via NKG2D. These small bi-specific proteins lack a Fc receptor, which avoids off-tumor toxicity due to potential interaction with Fc receptor expressing cells such as macrophages or dendritic cells. Clinical data using an anti-CD19-anti-CD3 bi-specific molecule demonstrated excellent efficacy at very low doses. The potential of these bi-specific molecules is to treat cancer through activation of a patient’s own T cells. Dr. Sentman’s research group is developing novel bi-specific molecules based on various NK cell receptor and their ligands, demonstrating efficacy in melanoma and lymphoma models, and investigating their mechanisms of action against different tumor types.

Novel cell based therapies: Dr. Sentman’s team is working on developing several new signaling platforms that can serve as the basis for adoptive cell therapies against cancer, autoimmunity, and infectious diseases. These platforms are designed to be used with many different recognition strategies to allow flexibility to create cell based therapies that bind to key targets and provide unique effector functions to modify local immunity.

Clinical development: Dr. Sentman is working in collaboration with Celdara Medical LLC and the Dana-Farber Cancer Center to move the NKG2D-based CAR into a Phase I clinical trial. He is also working with clinicians at Dartmouth-Hitchcock Medical Center and other collaborators to develop and move their other therapeutic ideas into clinical development. Several of these technologies have been patented or have patents pending. To inquire about licensing or collaborative opportunities, please contact Dr. Sentman or the Dartmouth Technology Transfer Office.

Selected Publications


Human CD4+CD25+ T cells expressing a chimeric antigen receptor against aberrant superoxide dismutase 1 trigger antigen-specific immunomodulation.
Graber DJ, Cook WJ, Sentman ML, Murad-Mabaera JM, Sentman CL
Cytotherapy. 2024 Feb;26(2):126-135. doi: 10.1016/j.jcyt.2023.11.007. Epub 2023 Dec 3.
PMID: 38043051

Superkine IL-2 and IL-33 Armored CAR T Cells Reshape the Tumor Microenvironment and Reduce Growth of Multiple Solid Tumors.
Brog RA, Ferry SL, Schiebout CT, Messier CM, Cook WJ, Abdullah L, Zou J, Kumar P, Sentman CL, Frost HR, Huang YH
Cancer Immunol Res. 2022 Aug 3;10(8):962-977. doi: 10.1158/2326-6066.CIR-21-0536.
PMID: 35696724

Engineering a natural ligand-based CAR: directed evolution of the stress-receptor NKp30.
Butler SE, Brog RA, Chang CH, Sentman CL, Huang YH, Ackerman ME
Cancer Immunol Immunother. 2022 Jan;71(1):165-176. doi: 10.1007/s00262-021-02971-y. Epub 2021 May 27.
PMID: 34046711

A Chimeric Antigen Receptor That Binds to a Conserved Site on MICA.
Cook WJ, Choi Y, Gacerez A, Bailey-Kellogg C, Sentman CL
Immunohorizons. 2020 Oct 9;4(10):597-607. doi: 10.4049/immunohorizons.2000041. Epub 2020 Oct 9.
PMID: 33037097

Toxicity Induced by a Bispecific T Cell-Redirecting Protein Is Mediated by Both T Cells and Myeloid Cells in Immunocompetent Mice.
Godbersen-Palmer C, Coupet TA, Grada Z, Zhang SC, Sentman CL
J Immunol. 2020 Jun 1;204(11):2973-2983. doi: 10.4049/jimmunol.1901401. Epub 2020 Apr 15.
PMID: 32295875

Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma.
Baumeister SH, Murad J, Werner L, Daley H, Trebeden-Negre H, Gicobi JK, Schmucker A, Reder J, Sentman CL, Gilham DE, Lehmann FF, Galinsky I, DiPietro H, Cummings K, Munshi NC, Stone RM, Neuberg DS, Soiffer R, Dranoff G, Ritz J, Nikiforow S
Cancer Immunol Res. 2019 Jan;7(1):100-112. doi: 10.1158/2326-6066.CIR-18-0307. Epub 2018 Nov 5.
PMID: 30396908

Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy.
Murad JM, Baumeister SH, Werner L, Daley H, Trebeden-Negre H, Reder J, Sentman CL, Gilham D, Lehmann F, Snykers S, Sentman ML, Wade T, Schmucker A, Fanger MW, Dranoff G, Ritz J, Nikiforow S
Cytotherapy. 2018 Jul;20(7):952-963. doi: 10.1016/j.jcyt.2018.05.001. Epub 2018 Jun 29.
PMID: 30180944

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies.
Murad JM, Graber DJ, Sentman CL
Best Pract Res Clin Haematol. 2018 Jun;31(2):176-183. doi: 10.1016/j.beha.2018.03.003. Epub 2018 Mar 27.
PMID: 29909918

T-bet promotes potent antitumor activity of CD4(+) CAR T cells.
Gacerez AT, Sentman CL
Cancer Gene Ther. 2018 Jun;25(5-6):117-128. doi: 10.1038/s41417-018-0012-7. Epub 2018 Mar 7.
PMID: 29515240

Chimeric antigen receptors with human scFvs preferentially induce T cell anti-tumor activity against tumors with high B7H6 expression.
Gacerez AT, Hua CK, Ackerman ME, Sentman CL
Cancer Immunol Immunother. 2018 May;67(5):749-759. doi: 10.1007/s00262-018-2124-1. Epub 2018 Feb 16.
PMID: 29453518

View more publications on PubMed