Peptide-pulsed MHC class II allogeneic dendritic cell vaccine has superior efficacy providing allogeneic help in a murine cancer model.

Allogeneic dendritic cell (DC) cancer vaccines present a promising alternative to autologous counterparts, offering an “off-the-shelf” solution for multiple patients and providing additional allogeneic help. We assessed the efficacy of a semi-allogeneic DC vaccine in comparison to a syngeneic one for tumor suppression. C57BL/6 mice were inoculated subcutaneously with human papillomavirus E6 and E7-expressing TC-1 cells. Syngeneic bone marrow DCs (BMDCs) were generated from C57BL/6 and semi-allogeneic BMDCs with a point mutation on either MHC class I or II were generated from B6.C-H2-K^bm1/By and B6(C)-H2-Ab1^bm12/KhEg, respectively. The TC-1-bearing mice were injected with syngeneic or semi-allogeneic BMDCs pulsed with H-2D^b-restricted E7_43-77 peptide. Compared with saline control, the MHC-I mutant BMDC vaccine reduced tumor growth no better than the syngeneic one. However, the MHC-II mutant BMDC vaccine was significantly better at delaying tumor growth. CD4+ or CD8+ T cell depletion showed that the syngeneic BMDC vaccine worked independently of CD4+ T cells, but the enhanced activity of the MHC-II mutant BMDC vaccine was dependent on CD4+ T cells at an early stage. Surprisingly, later depletion of CD4+ T cells improved vaccine efficacy, and this was confirmed to be due to Treg depletion. Thus, MHC class II allogeneic BMDCs proved more effective by inducing early allogeneic CD4+ T cell help, and this effect can by further enhanced by Treg depletion at a later stage.