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

TLDR

Cytotoxic T‑lymphocyte peptide epitopes can immunize mice against lethal viral infections, and HPV is present in over 90 % of cervical cancers. The study aimed to test whether CTL peptide immunization could prevent virus‑induced tumors by generating an HPV‑transformed B6 tumor cell line. The authors screened 240 overlapping peptides from HPV16 E6/E7 for H‑2Kb/H‑2Db binding, identified the high‑affinity H‑2Db epitope E7 49‑57 (RAHYNIVTF), and used it to vaccinate mice. Vaccination with the E7 49‑57 peptide protected mice from HPV16‑transformed tumor challenge and elicited CTLs that lysed tumor cells in vitro.

Abstract

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 .