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ASH 2020 | Engineering multi-antigenic CAR T-cells for AML
Sara Ghorashian, FRCPath, PhD, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, discusses the development of multi-antigenic CAR T-cells to treat acute myeloid leukemia (AML). Through addition of nanobody binding domains, CAR T-cells were engineered to be specific to three AML-associated antigens with broad expression on AML blasts and leukemic stem cells: CD33, CD123 and CLL1. The multi-target approach aimed to overcome antigen negative escape and intra-tumor heterogeneity which is high in AML. Experiments proved that each nanobody binding domain could successfully bind to its antigen, and the CAR T-cells demonstrated cytolytic activity against engineered target cells expressing each of the three antigens. The activity of the multi-antigenic CAR T-cells was shown to be at least as potent as single antigen nanobody CAR T-cells. Future tests will aim to optimize responses with AML cells in vivo. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
