Vectorized Treg-depleting αCTLA-4 elicits antigen cross-presentation and CD8⁺ T cell immunity to reject 'cold' tumors.

ABSTRACT:

Background

Immune checkpoint blockade (ICB) is a clinically proven concept to treat cancer. Still, a majority of patients with cancer including those with poorly immune infiltrated 'cold' tumors are resistant to currently available ICB therapies. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is one of few clinically validated targets for ICB, but toxicities linked to efficacy in approved αCTLA-4 regimens have restricted their use and precluded full therapeutic dosing. At a mechanistic level, accumulating preclinical and clinical data indicate dual mechanisms for αCTLA-4; ICB and regulatory T cell (Treg) depletion are both thought to contribute efficacy and toxicity in available, systemic, αCTLA-4 regimens. Accordingly, strategies to deliver highly effective, yet safe αCTLA-4

SUBMITTER: Semmrich M 

PROVIDER: S-EPMC8783833 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature