Engineering single-vector logic-gated CAR T cells with transgene sizes beyond current limitations.

ABSTRACT:

Background

Engineering chimeric antigen receptor (CAR) T cells with logic-gated synthetic Notch (synNotch) receptor circuits can enhance specificity and mitigate on-target/off-tumor toxicity. However, the conventional synNotch system uses two lentiviral vectors encoding the synNotch receptor and inducible CAR, requiring dual transduction and cell sorting, which limits clinical translation. Integrating the synNotch-CAR circuit into a single lentiviral vector could overcome this limitation, yet manufacturing CAR T cells with large transgenes remains challenging, as increasing transgene size drastically reduces lentiviral titers and T cell transduction efficiency. Current production workflows compensate for low transduction efficiency by sorting transduced cells, further impeding clin

SUBMITTER: Rommel PC 

PROVIDER: S-EPMC12815206 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature