Peptide-pulsed MHC class II mutant dendritic cell vaccine has superior efficacy in a murine tumor model.

Abstract

Abstract Autologous dendritic cell (DC) vaccines with tumor antigens have been used clinically with limited therapeutic effects. Semi-allogeneic DC-based immunotherapy is still controversial, but it can be an alternative source and more attractive than autologous DC vaccines because the “off-the-shelf” DCs can be used for multiple patients without lengthy individual manufacturing time and may provide additional “allogeneic help”. This study aims to compare efficacy of syngeneic DC vaccines and semi-allogeneic DC vaccines and determine whether a therapeutic semi-allogeneic DC vaccine is more efficacious in tumor suppression. Female C57BL/6 mice were inoculated subcutaneously with human papillomavirus E6 and E7-expressing TC-1 cells. Syngeneic bone marrow dendritic cells (BMDCs) were generated from C57BL/6 and semi-allogeneic BMDCs were generated from two mouse strains, B6.C-H2-K bm1/ByJ and B6(C)-H2-Ab1 bm12/KhEgJ which had limited point mutations in the MHC class I H2-K ballele or H2-lA bMHC class II allele, respectively. Each BMDC was pulsed with H-2D b-restricted E7 43–77peptide and matured before injection. The mice received 4 intradermal injections of syngeneic or one of the semi-allogeneic E7-pulsed BMDC vaccines starting 8–9 days after the TC-1 implantation. Compared with saline control, the MHC class I mutant BMDC vaccine had efficacy similar to the syngeneic BMDC vaccine in suppressing TC-1 tumor growth. However, the MHC class II mutant BMDC vaccine had efficacy significantly superior to that of the other BMDC vaccines. Thus, MHC class II semi-allogeneic BMDCs may be more effective than syngeneic DC-based cancer vaccines, presumably because the class II alloantigens induce additional T cell help for anti-tumor immunity.