Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.

ABSTRACT:

Background

Chimeric antigen receptor (CAR)-T cells face many obstacles in solid tumor therapy, including heterogeneous antigen expression and inefficient T cell persistence. Guanylyl cyclase C (GUCY2C) has been identified as a suitable tumor antigen for targeted therapy due to its intestinal-restricted expression pattern in normal tissues and steady overexpression in gastrointestinal tumors, especially colorectal cancer. An antigen-sensitive and long-lasting CAR-T cell targeting GUCY2C was investigated in this study.

Methods

Using constructed tumor cell lines with various GUCY2C expression densities, we screened out an antigen-sensitive single chain variable fragment (scFv) that enabled CAR-T cells to efficiently eradicate the GUCY2C lowly expressed tumor cells. CAR-T cells

SUBMITTER: Qi C 

PROVIDER: S-EPMC11459315 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature