HVEM costimulatory domain boosts CAR T cell efficacy against solid tumors via enhanced TRAF-mediated TNF signaling.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) T cell therapy has shown success in hematological malignancies, but its efficacy against solid tumors remains limited. Herpesvirus entry mediator (HVEM), a co-stimulatory molecule, enhances CAR T cell activity, though the underlying mechanisms are unclear. This study investigates how HVEM-based CAR T cells outperform those using 4-1BB in solid tumor models.

Methods

Second-generation CAR T cells targeting carbonic anhydrase IX (CAIX) were engineered with either 4-1BB, wild type (WT) HVEM, or AVEE mutation (MUT) HVEM co-stimulatory domains. In vitro cytotoxicity, cytokine release, and signaling pathways were assessed using real-time cellular analysis, ELISA, and Western blotting. RNA sequencing and gene set enrichment analysis (GSEA)

SUBMITTER: Sun S 

PROVIDER: S-EPMC12870389 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature