Antibody-mediated Delivery of TAPBPR Enables the Redirection of Virus-Specific T Cell Responses to Tumour Cells

Abstract Low tumour immunogenicity is a major hurdle to overcome in the treatment of cancers with immunotherapies. Here, we reveal a novel therapeutic approach to increase tumour immunogenicity. By delivering the major histocompatibility complex class I (MHC-I) peptide exchange catalyst TAPBPR in an antibody-mediated manner onto the plasma membrane of tumour cells, extracellular MHC-I become highly peptide-receptive. Upon exposure to low doses of exogenous peptide, MHC-I molecules on tumour cells are efficiently loaded with immunogenic antigens, including those derived from human cytomegalovirus and Epstein-Barr virus. TAPBPR-antibody fusion proteins were delivered specifically to tumours in vivo. Finally, antigen-specific CD8+ T cells respond to tumour cells in a targeted manner and can mediate killing of antibody target-positive cells. As memory T cells specific for previously encountered common viruses patrol tumours, TAPBPR-based therapeutics could offer an attractive means to redirected virus-specific T cells against tumours in the fight against cancer.