Kurzfassung

Adoptive cellular therapy (ACT) using chimeric antigen receptor (CAR) redirected human T lymphocytes has achieved remarkable clinical outcome for acute lymphocytic leukemia and also shows great promise for e.g. multiple myeloma. However, suitable antigens for a specific CAR therapy in acute myeloid leukemia (AML) without significant off-target effects are still warranted as e.g. CD33 and CD123 are also expressed on hematopoietic stem cells (HSC). In contrast, B7H6, a member of the B7 family,...Adoptive cellular therapy (ACT) using chimeric antigen receptor (CAR) redirected human T lymphocytes has achieved remarkable clinical outcome for acute lymphocytic leukemia and also shows great promise for e.g. multiple myeloma. However, suitable antigens for a specific CAR therapy in acute myeloid leukemia (AML) without significant off-target effects are still warranted as e.g. CD33 and CD123 are also expressed on hematopoietic stem cells (HSC). In contrast, B7H6, a member of the B7 family, is frequently expressed on various cancers including patient-derived (primary) AML blasts and e.g. melanoma but not found on normal tissues and recognized by the natural killer (NK) cell activating receptor NKp30.
In this study, we therefore evaluate human T cells as well as CRISPR/Cas9 engineered TCR- T cells expressing two different 2nd generation NKp30 CARs for effective antileukemic immunity to AML in vitro and in vivo using a patient-derived AML xenograft (PDX) model. Additionally, antitumoral responses of NKp30 CAR T cells to melanoma are being examined.
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