Dr. Ryan K. Alexander is an inaugural fellow in the CRI Irvington Postdoctoral Fellowship to Promote Racial Diversity. He is is exploring a modular strategy for targeting pancreatic cancer with nanobody-based CAR T cells and macrophages.
Pancreatic cancer is one of the deadliest cancers, and is often resistant to both chemotherapy and immunotherapy. Chimeric antigen receptor (CAR) T cells and macrophages, which can kill cancer cells in complementary ways, are emerging important tools for cancer immunotherapy. While CAR T cells been successful against blood cancers, their use against solid tumors lags behind, in part due to difficulties with getting the cancer-targeting CARs to be properly expressed on the cell surface.
In the laboratory of Hidde Pleogh, Ph.D., at Boston Children’s Hospital, Dr. Alexander is exploring the use of novel CARs developed by his team to overcome the hurdles. These CARs use alpaca antibody-derived nanobodies, which are smaller than antibodies and are displayed more efficiently on the cell surface, and are designed to target proteins that are highly and selectively expressed by pancreatic tumors compared to healthy tissue. They’re also less likely to be recognized as “foreign” by the immune system and attacked. Specifically, Dr. Alexander will be investigating whether these nano-CAR T cells and nano-CAR macrophages can synergize in combination to overcome normally resistant pancreatic tumors in mice.
Projects and Grants
A modular strategy for targeting pancreatic cancer with nanobody-based CAR T cells and macrophages
Boston Children’s Hospital | Pancreatic Cancer | 2021 | Hidde Ploegh, Ph.D.
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