DAP12-associated synthetic antigen receptors enable multi-targeting of T cells with independent chimeric receptors in a small genetic payload.

ABSTRACT: We describe a series of DAP12-associated receptors that can be used to achieve multi-targeting within a small genetic payload. Empirical evaluation of scaffold/binder combinations is required to define the optimal synthetic receptor configuration. When two DAP12-associated synthetic receptors were expressed in T cells from a single vector, the surface levels of individual receptors was reduced when compared to T cells engineered with vectors that express a single receptor. The reduction in receptor expression had a pronounced effect on early, but not late, signaling events and primarily affected cytokine production. The functional deficiency was overcome by increasing synthetic receptor levels demonstrating that there is no fundamental issue related to co-expression of multiple DAP12-assoc

SUBMITTER: Moore AE 

PROVIDER: S-EPMC11978328 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature