The development of therapeutic
vaccines has important implications for the treatment of
cancer patients. Here we investigate whether human papillomavirus (HPV) E7
subunit vaccines can enhance
tumor radioresponse using an established
cervical cancer animal model. Radiation plus E7
subunit vaccines improved complete response, cure, and recurrence rates of
tumors dramatically compared with single
therapy alone. In particular, both components of the E7
subunit vaccines (E7
protein and CpG-
oligodeoxynucleotide) were required for the induction of
antigen (Ag)-specific cytotoxic T-lymphocyte (CTL) responses and for therapeutic synergy with
radiotherapy. Moreover, with combined
therapy the radiation dose could be reduced by 16 Gy to achieve an equivalent anti-
tumor efficacy to
radiation treatment alone. This therapeutic synergy was found to be mediated by CD8(+) CTLs and was concomitant with histological changes (presence of apoptotic bodies and multinucleated giant cells; heavy infiltration of lymphocytes), as determined by in vivo T-cell depletion and histological analysis. Finally, phenotypic changes of radiated
tumors and their increased sensitivity to CTL-mediated killing appeared to be responsible for therapeutic synergy. These results show that E7
subunit vaccines act as a potent enhancer of
tumor radioresponse and that this is mediated by increased sensitivity of radiated
tumors to CTL-mediated killing. This study further suggests that E7-targeted therapeutic
vaccines have the potential to improve
radiotherapy in patients with
cervical cancer.