IMMUNIZATION WITH HUMAN-PAPILLOMAVIRUS TYPE-16 (HPV16) ONCOPROTEIN-LOADED DENDRITIC CELLS AS WELL AS PROTEIN IN ADJUVANT INDUCES MHC CLASS I-RESTRICTED PROTECTION TO HPV16-INDUCED TUMOR-CELLS

Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targe ts for T-cell-based immunotherapy of cervical cancer, In this study, w e demonstrate that dendritic cells (DCs) pulsed with HPV16 E7 protein are not only recognized in vitro by E7-specific CTLs but also elicit E 7-specific CTL responses in vivo, associated with protection against a challenge with syngeneic HPV16-induced tumor cells, Vaccination with soluble E7 protein in incomplete Freund's adjuvant likewise induces E7 -specific CTL responses associated with tumor protection, The presence of HPV16 E7-specific CTLs in vivo and the observation that depletion of CD8+ cells completely abolishes tumor protection demonstrate that C TLs are the major effector cells in mediating antitumor activity, The in vivo involvement of DCs in the activation of protective CTLs is sug gested by the surface display of E7 peptide-loaded MHC class I molecul es on these cells after E7 protein immunization, These data show that HPV16 E7 protein-pulsed DCs, as well as the administration of E7 prote in antigen in adjuvant, can effectively stimulate tumor-specific MHC c lass I-restricted CD8+ T-cell-mediated protective immunity to HPV16-in duced cancers.