Functional screening of TCR-like antibodies using STAR-T cell library for cancer immunotherapy

ABSTRACT: Adoptive T-cell therapies engineered with T-cell receptors (TCRs) or TCR-like antibodies have shown considerable promise in cancer immunotherapy. However, identifying tumor antigen-specific TCR-like antibodies, particularly against human leukocyte antigen-presented neoantigens, remains challenging. Here, we present a function-based, rather than affinity-based, antibody screening platform utilizing Synthetic T-cell receptor and Antigen Receptor (STAR)-T cell libraries. We found that antigen engagement in STAR-T cells triggers synchronous receptor endocytosis and T-cell activation, and we integrated these paired processes into an Endocytosis-Activation (E-A) functional readout for antibody screening. Applying E-A functional screening, we rapidly identified multiple nanobodies targeting the c

SUBMITTER: Xin Lin 

PROVIDER: S-SCDT-10_1038-S44321-026-00455-Z | biostudies-other |

REPOSITORIES: biostudies-other