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Charles L. Sentman, PhD

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Professional Interests

Dr. Sentman directs the Center for Synthetic Immunity and is a Professor of Immunology at Dartmouth. His research is focused on the development and use of novel immune cell engineering approaches as treatments for cancer, neurodegeneration, and other diseases. Dr. Sentman's research interests began on 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, neurodegenerative disease and autoimmunity. There are several major areas of research: chimeric receptor based immunotherapy, bi-specific antibody targeting of tumors, bispecific engagers, and development of novel CAR Treg based therapies for neurodegenerative diseases, including Alzheimer's disease and ALS.

Dr. Sentman’s lab has developed novel chimeric antigen receptors based on NK cell receptors as a means to treat cancer. These CARs are formed by a fusion of NKG2D with a cytoplasmic signaling domain of CD3zeta. 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. 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.

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 engagers based on the scFv from anti-CD3 and tumor ligands, such as MICA, B7H6, and ULBPs. The potential of bi-specific engagers 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 CAR Treg cell based therapies: Dr. Sentman’s team is working on developing CAR Tregs to treat ALS, Alzheimer's Disease and Parkinson's disease. These CAR Tregs localize to the CNS and are further engineered to enhance the natural anti-inflammatory and immunomodulatory activity of Tregs.

Clinical development: Dr. Sentman is working in collaboration with Celdara Medical LLC and Black Bear Bio to move these ideas into clinical testing. 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.

Dr. Sentman has more than 30 issued US Patents and is a member of the National Academy of Inventors. To inquire about licensing or collaborative opportunities, please contact Dr. Sentman or the Dartmouth Technology Transfer Office.

Biography

Dr. Sentman directs the Center for Synthetic Immunity and is a Professor of Immunology at Dartmouth. His research is focused on the development and use of novel immune cell engineering approaches as treatments for cancer, neurodegeneration, and other diseases. He and his team have been working with chimeric antigen receptors (CARs) since 2003 with a focus on NK cell and T cell-based therapies. He has thirty issued US patents, more than one hundred scientific publications, and has co-founded two therapeutics companies. He trained at UT Southwestern, Washington University, and the Karolinska Institute.