Antibody-mediated delivery of a viral MHC-I epitope into the cytosol of target tumor cells repurposes virus-specific CD8⁺ T cells for cancer immunotherapy.

ABSTRACT:

Background

Redirecting pre-existing virus-specific cytotoxic CD8⁺ T lymphocytes (CTLs) to tumors by simulating a viral infection of the tumor cells has great potential for cancer immunotherapy. However, this strategy is limited by lack of amenable method for viral antigen delivery into the cytosol of target tumors. Here, we addressed the limit by developing a CD8⁺ T cell epitope-delivering antibody, termed a TEDbody, which was engineered to deliver a viral MHC-I epitope peptide into the cytosol of target tumor cells by fusion with a tumor-specific cytosol-penetrating antibody.

Methods

To direct human cytomegalovirus (CMV)-specific CTLs against tumors, we designed a series of TEDbodies carrying various CMV pp65 antigen-derived peptides. CMV-specific CTLs

SUBMITTER: Jung K 

PROVIDER: S-EPMC9027861 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature