靶向 T 细胞受体 β 链的 CAR-T 细胞对抗 T 细胞恶性肿瘤

The success of chimeric antigen receptor (CAR) T cells in treating B cell malignancies comes at the price of eradicating normal B cells. Even though T cell malignancies are aggressive and treatment options are limited, similar strategies for T cell malignancies are constrained by the severe immune suppression arising from bystander T cell aplasia.

Here, we show the selective killing of malignant T cells without affecting normal T cell-mediated immune responses in vitro and in a mouse model of disseminated leukemia.

Further, we develop a CAR construct that carries the single chain variable fragment of a subtype-specific antibody against the variable TCR -chain region.

We demonstrate that these anti-V 8 CAR-T cells are able to recognize and kill all V 8 + malignant T cells that arise from clonal expansion while sparing malignant or healthy V 8 - T cells, allowing sufficient T cell-mediated cellular immunity. In summary, we present a proof of concept for a selective CAR-T cell therapy to eradicate T cell malignancies while maintaining functional adaptive immunity, which opens the possibility for clinical development.