Cancer immunotherapy based on cytotoxic CD8 T lymphocyte (CTL)-mediated tumor recognition and elimination has shown remarkable anticancer efficacy. Nonetheless, the suppression or absence of antitumor CTLs in the tumor microenvironment (TME) and tumor immune escape (evasion of an antitumor CTL response) limit the clinical efficacy in many patients with solid tumors. 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 tumor.
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 The TEDbody technology can be utilized for cytosolic delivery of other (nonviral) MHC-I antigens, such as tumor neoantigens, into tumors lacking tumor antigens suitable for immunotherapy and has good potential for expanding the current arsenal of cancer immunotherapies.