krn-7000 and Papillomavirus-Infections

CD8+ T cell-mediated immune response plays a major role in the clearance of virus-infected cells, including human papillomavirus (HPV). The effective treatment of women with normal cytology but persistent high risk-HPV infection or with low-grade intraepithelial lesions could take advantage of novel strategies based on vaccination with viral immunological targets with a wide spectrum of cross-protection. The helicase E1, expressed early during viral replication in HPV infection, is among the most conserved papillomavirus proteins, which makes it a good vaccine candidate. In the present study, we examined E1-specific CD8+ T cell and NK immune responses in a mouse model with α-galactosylceramide (α-GalCer) as an adjuvant. We found that mice immunized with E1 combined with α-GalCer elicited an E1-specific CD8+ T and NK cell cytotoxic responses, which correlated with growth inhibition of grafted melanoma B16-F0 cells expressing E1, both in prophylactic and therapeutic protocols.

Topics: Adjuvants, Immunologic; Animals; Cancer Vaccines; Cytotoxicity, Immunologic; Female; Galactosylceramides; Human papillomavirus 18; Humans; Killer Cells, Natural; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Oncogene Proteins, Viral; Papillomavirus Infections; T-Lymphocytes, Cytotoxic; Transplants; Tumor Cells, Cultured; Vaccination