Dendritic cell CD40 targeting vaccines elicit CD8+ T cell-mediated therapeutic immunity against cancers

Abstract

Abstract Dendritic cells (DCs) are major antigen-presenting cells that can efficiently cross-prime antigen-specific cytotoxic T lymphocytes (CTLs). Antigen targeting to DCs through surface receptors is therefore a promising strategy to mount CD8+ CTL-mediated immunity against viral infections and cancers. We have previously reported that viral (Influenza HA and NP) and tumor antigen (MART-1) targeting to human DCs via CD40 resulted in greater antigen-specific functional CD8+ CTL responses in vitro. In this study, we have tested CD40 targeting prototype vaccines for HPV16-associated malignancies (anti-CD40-HPV16.E6/7) and prostate cancer (anti-CD40-PSA). Our data show that both anti-CD40-HPV16.E6/7 and anti-CD40-PSA prototype vaccines are able to activate antigen-specific CD8+ T cells in the blood of head-and-neck and prostate cancer patients, respectively. We further demonstrate that the in vivo administration of anti-CD40-HPV16.E6/7 or anti-CD40-PSA plus poly(I:C) can mount tumor-specific CTL-mediated therapeutic and preventive immunity against the respective tumors in human CD40 transgenic mice. Data from this study support the clinical development of CD40 targeting vaccines against cancers and viral infections.