TUMOR-REGRESSION IN MICE FOLLOWING VACCINATION WITH HUMAN-PAPILLOMAVIRUS E7 RECOMBINANT PROTEIN IN PROVAX(TM)

Induction of CD8(+) cytotoxic T lymphocytes (CTLs) specific for human papillomavirus (HPV) antigens provides an attractive strategy for immu notherapy of HPV-related cancers in humans. In this study, we investig ated the potential of utilizing soluble E7 protein of HPV 16 in an adj uvant formulation, PROVAX(TM) as a vaccine against a progressively gro wing E7 transfected K1735-X21 (H-2(k)) metastatic melanoma cells (HOPE 2) in a mouse model. Vaccination of HOPE2 tumor bearing mice (C3H) wit h E7 protein in PROVAX resulted in significant inhibition of tumor gro wth, compared to mice vaccinated with E7 in Alum or saline. In vivo de pletion of CD8(+) or CD4(+) cells indicated that CD8(+) cells are the major effector cells in mediating the anti-tumor activity in this mode l. Furthermore, E7-specific CTL activity in vitro was detected in tumo r bearing mice vaccinated with E7-PROVAX. Our studies suggest that rec ombinant HPV antigens in combination with PROVAX could serve as an eff ective subunit vaccine to stimulate tumor specific CD8(+) T cell media ted immunity against HPV-related cancers.