Vaccination with cytotoxic T lymphocyte epitope‐containing peptide protects against a tumor induced by human papillomavirus type 16‐transformed cells

Abstract

Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immunization of mice against lethal virus infection. To study whether this approach can be successful against virus‐induced tumors we generated a B6 (H‐2 b) tumorigenic cell line transformed by human papillomavirus (HPV). This virus is detected in over 90% of all human cervical cancers. To identify vaccine candidates, we generated a set of 240 overlapping peptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. These peptides were tested for their ability to bind H‐2K b and H‐2D b MHC class I molecules. Binding peptides were compared with the presently known peptide‐binding motifs for H‐2K b and H‐2D b and the predictive value of these motifs is shortly discussed. The high‐affinity H‐2D b‐binding peptide and putative CTL epitope E 7 49‐57 (RAHYNIVTF) was used in vaccination studies against HPV 16‐transformed tumor cells. Immunization with peptide E 7 49‐57 rendered mice insensitive to a subsequent challenge with HPV 16‐transformed tumor cells in vivo, and induced a CTL response which lysed the tumor cells in vitro.