Abstract IA26: Combination immunotherapy of cancer caused by human papilloma virus

Abstract

We have completed a chemo-immunotherapy study in 70 patients with late stage HPV16+ cervical cancer. Three HPV16-SLP vaccine doses, consisting of 13 overlapping peptides covering the amino acid sequence of the oncogenic proteins E6 and E7 of HPV16, were given 2 weeks after the second, third and fourth cycle of standard chemotherapy (carboplatin, AUC 6; paclitaxel 175 mg/ m2). The vaccine was administered subcutaneously as an emulsion in adjuvant Montanide ISA-51. Cohorts of 12 patients were vaccinated with each of 4 dose levels (20, 40, 100 and 300 µg/ per peptide) of 13 overlapping HPV16 synthetic long peptides (HPV16-SLP) together covering the E6 and E7 protein sequence. Two additional cohorts of 6 patients each were vaccinated with the most promising doses of 40 and 100 µg/ peptide. A marked and significant positive correlation was observed between the strength of the vaccine-induced T cell immune response and overall survival. No such correlation was observed between the strength of the T cell response against common recall antigens and survival. In addition a remarkably high proportion of patients survived beyond 2 years after the start of therapy. We also completed a combination study of this vaccine with checkpoint blocker nivolumab (anti-PD-1) in patients with incurable HPV16+ oropharyngeal cancer. Of 22 treated patients, 2 achieved a durable complete clinical response (CR) by resist criteria and 6 a partial response (PR). The overall response rate was 36%, approximately twice that reported for nivolumab as monotherapy in a similar category of patients with oropharyngeal cancer. This combination treatment was associated with robust HPV16 E6/E7-specific T cell responses. Citation Format: Cornelis J.M. Melief. Combination immunotherapy of cancer caused by human papilloma virus [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA26.