Adenovirus-assembled DC vaccine induces dual-targeting CTLs for tumor antigen and adenovirus to eradicate tumors
ABSTRACT
The dendritic cell (DC) vaccine is a promising cancerimmunotherapy strategy, but its efficacy in treating the solid tumor is limited. To overcome this limitation, an oncolytic adenovirus (OAV-IL-12) was developed to enhance antigen targeting ability of adenovirus-assembled DC vaccine (DCs-CD137L/CAIX) for renal carcinoma treatment. Peritumoral administration of OAV-IL-12 increased the number of tumor-infiltrating DCs and their subsets (CD8DCs and CD103DCs). Combining OAV-IL-12 with DCs-CD137L/CAIX significantly inhibited the growth of subcutaneous tumors by inducing potent cytotoxic T lymphocyte (CTL) effect and improving the immune infiltration in tumor lesions. Interestingly, this treatment also reduced tumor growth distal to the OAV-IL-12 injecting side via eliciting a systemic CTL response. Furthermore, OAV-IL-12 potentiated DCs-CD137L/CAIX treatment induced dual CTL responses against both CAIX and adenovirus antigens. The therapeutic benefits of this treatment approach mainly relied on multifunctional CD8T cell immune responses, as indicated by the depletion assay. Moreover, OAV-IL-12 potentiated DCs-CD137L/CAIX treatment generated a long-lasting protective effect against tumors by inducing memory CD8T cell immune responses. These results suggest that the effective tumor targeting of the adenovirus-based DC vaccine, boosted by OAV-IL-12, is a promising treatment approach for renal carcinoma and other solid tumors.