Overcoming Resistance to CAR-T Cell Therapy due to Antigen Loss or Modulation by New Chimeric Receptors Targeting Intracellular-Derived HLA Peptidome
Grant Amount: NIS 1.925 Million
About the Project
CAR T cells are immune cells collected from patients and engineered to express an antibody, which is directed specifically at the tumor. The most robust clinical data is derived from patients with acute lymphoblastic leukemia, treated with CAR T cells directed at the leukemia marker CD19. While most patients are initially cured with this form of treatment, a significant proportion of them will experience relapse of their cancer with the leukemia cells having lost CD19 expression, thus becoming “invisible” to the antibody. We have been able to identify fragments of CD19 which are still presented on the cell surface as peptide-HLA complexes. These short peptides are presented even at the time of relapse when the full-length CD19 is no longer expressed. Our laboratory designs a different kind of antibody, which can identify these fragments of CD19 and promote killing of the cancer cells. This may lead to a new treatment strategy for leukemia that has relapsed following CAR T cell therapy.

This research is conducted in collaboration with the Rambam medical Center bio-bank for the purpose of obtaining bone marrow samples from patients with B cell leukemia.
Research Team
Prof. Yoram Reiter
Laboratory of Molecular Immunology and Immunotherapy, Technion Institute of Technology
Prof. Myriam Ben-Arush
Department of Pediatric Hematology-Oncology, Rambam Medical Center
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