XCL1-secreting CEA CAR-T cells enhance endogenous CD8⁺ T cell responses to tumor neoantigens to confer a long-term antitumor immunity.

ABSTRACT:

Background

Therapeutic efficacy of carcinoembryonic antigen (CEA)-specific chimeric antigen receptor (CAR) T cells against colorectal cancer (CRC) remains limited due to the unique characteristics and distinct microenvironments of tumor tissues. We modified CEA-specific CAR-T cells, aiming to stimulate endogenous CD8⁺ T cell responses against neoantigens that were derived from CEA-positive tumors destroyed by the CAR T cells.

Methods

In a conventional CEA CAR (reg-CAR), we modified it to express lymphotactin XCL1 and interleukin (IL)-7 genes, constructing a modified 7XCL1-CAR. By generating the CEA-specific 7XCL1-CAR T cells, we assessed their antitumor efficacy against CRC cells with varying levels of CEA expression, both in cell-cultures and in two strains of tu

SUBMITTER: Li XN 

PROVIDER: S-EPMC11749649 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature