CAR Binders Affect CAR T-cell Tonic Signaling, Durability, and Sensitivity to Target.

ABSTRACT: Patients can develop human anti-mouse immune responses against CD19-specific chimeric antigen receptor (CAR) T cells due to the use of a murine CD19-specific single-chain variable fragment to redirect T cells. We screened a yeast display library to identify an array of fully human CD19 single-chain variable fragment binders and performed a series of studies to select the most promising fully human CAR. We observed significant differences in the ability of CARs employing these CD19 binders to be expressed on the cell surface, induce tonic signaling, redirect T-cell function, mediate tumor killing, recognize lower levels of CD19 antigen, and maintain function upon continuous antigen exposure. From this initial analysis, CAR T cells using two binders (42 and 52) were selected for additional s

SUBMITTER: Shukla D 

PROVIDER: S-EPMC12137003 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature