Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies.

ABSTRACT: Bispecific antibodies (biAbs) used in cancer immunotherapies rely on functional autologous T cells, which are often damaged and depleted in patients with haematological malignancies and in other immunocompromised patients. The adoptive transfer of allogeneic T cells from healthy donors can enhance the efficacy of biAbs, but donor T cells binding to host-cell antigens cause an unwanted alloreactive response. Here we show that allogeneic T cells engineered with a T-cell receptor that does not convert antigen binding into cluster of differentiation 3 (CD3) signalling decouples antigen-mediated T-cell activation from T-cell cytotoxicity while preserving the surface expression of the T-cell-receptor-CD3 signalling complex as well as biAb-mediated CD3 signalling and T-cell activation. In mice wi

SUBMITTER: Kapetanovic E 

PROVIDER: S-EPMC11668682 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature