Specific targeting of cancer vaccines to antigen-presenting cells via an endogenous TLR2/6 ligand derived from cysteinyl-tRNA synthetase 1

Abstract

Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll- like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly fi cantly enhanced antitumor activity in vivo compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. fi cacy. Specifically, fi cally, the conjugation of UNEC1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific fi c delivery to dendritic cells and E7 antigen-specific fi c T cell responses, and antitumor efficacy fi cacy in vivo compared with the noncovalent combination of the two peptides. These fi ndings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific fi c delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines.