Detection of T helper responses, but not of human papillomavirus-specific cytotoxic T lymphocyte responses, after peptide vaccination of patients with cervical carcinoma

Human papillomavirus type 16 (HPV16)-encoded E7 oncoprotein is constitutive ly expressed in cervical carcinoma cells and is required for cellular trans formation to be maintained. The E7 protein, therefore, forms an attractive target for T-cell-mediated immune intervention to prevent or treat HPV16(+) tumors. The authors performed a peptide-based phase I/II vaccination trial to induce anti-tumor immune responses in patients with recurrent or residu al cervical carcinoma. Fifteen HLA-A*0201* patients with HPV16(+) cervical carcinoma received vaccinations with synthetic peptides representing 2 HPV1 6 E7-encoded, HLA-A*0201-restricted cytotoxic T lymphocyte epitopes and a p an-HLA-DR-binding T-helper epitope, PADRE, in adjuvant. No signs of toxicit y were observed. Two patients had stable disease for more than 1 year after vaccination, 3 patients died of the disease during or shortly after the va ccination period, and 10 patients maintained progressive cervical carcinoma . Specific immune responses directed against the vaccine components were an alyzed in peripheral blood samples. No cytotoxic T lymphocyte responses aga inst the HPV16 E7 peptides were detectable. After vaccination, strong PADRE helper peptide-specific proliferation was detected in 4 of 12 patients. In conclusion, peptide vaccination with 2 HPV16 E7 cytotoxic T lymphocyte epi topes and a universal T helper epitope is well tolerated by patients with a dvanced cervical carcinoma. Despite a reduction of in vitro cytolytic or pr oliferative recall responses to some, but not all, conventional antigens in this patient group, peptide-specific proliferative responses were induced in 4 patients. Based on the current study, it is now feasible to perform pe ptide vaccination in earlier stages of HPV16-induced cervical disease.