Engineered SH3-Derived Sherpabodies Function as a Modular Platform for Targeted T-cell Immunotherapy.

ABSTRACT: Engineered T-cell therapies have emerged as a promising approach for cancer treatment, yet their application to solid tumors remains challenging because of the limited specificity and persistence of current antigen recognition strategies. In this study, we introduce sherpabodies, engineered from a human SH3 domain scaffold, as a class of antibody-mimetic proteins capable of precise tumor-associated antigen (TAA) recognition. A phage display library identified sherpabodies against a panel of popular TAAs, which were subsequently incorporated into second-generation chimeric antigen receptor (CAR) constructs that were termed sherpabody-guided CARs (SbCAR). These SbCARs demonstrated potent in vitro specificity and cytotoxicity against solid cancer TAAs, without cross-reactivity to closely rela

SUBMITTER: Hernandez-Lopez RA 

PROVIDER: S-EPMC12081183 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature