Chronic antigen stimulation in melanoma induces T cell exhaustion and limits efficacy of T cell bispecific therapies.

ABSTRACT: T cell bispecific antibodies (TCBs) have demonstrated promising results in patients with solid tumors, yet the immunological mechanisms influencing their efficacy require further investigation. T cell exhaustion, induced by prolonged antigen exposure, is known to compromise T cell-based immunotherapies, but its effect on TCB efficacy remains unclear. Herein, we assessed the TCB efficacy on tumor-specific T cells, emphasizing their functional status. Utilizing an immunocompetent mouse model with melanoma expressing an immunogenic antigen, we showed that tumor-specific T cells acquire an exhausted phenotype and fail to expand under TCB treatment. Both mouse and human tumor-specific T cells in vitro demonstrated that chronically stimulated T cells exhibit a reduced response to TCBs. Th

SUBMITTER: Hutter-Karakoc I 

PROVIDER: S-EPMC12382474 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature