Vaccination with synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust E7-specific CD8 T cell responses and TC-1 tumor eradication

• Published in: BMC cancer 2019-06, Vol.19 (1), p.540-540, Article 540
• Main Authors: Maynard, Sean K, Marshall, Jason D, MacGill, Randall S, Yu, Li, Cann, Jennifer A, Cheng, Lily I, McCarthy, Michael P, Cayatte, Corinne, Robbins, Scott H
• Format: Article
• Language: English
• Subjects: Adenoviruses; Adjuvants, Immunologic; Agonists; Animal models; Animals; Antigenic determinants; Antigens; Cancer; Cancer immunotherapy; Cancer vaccines; Cancer Vaccines - immunology; Care and treatment; CD8 antigen; Cell culture; Cell Line, Tumor; CpG islands; CpG Islands - immunology; Cytokines; Cytotoxicity; Disease Models, Animal; Emulsions - chemistry; Epitopes; Epitopes - immunology; Female; Herpes viruses; Histocompatibility Antigens Class I - immunology; Human papilloma virus antigen E7 (HPV E7); Human papillomavirus; Immunogenicity; Immunologic Memory; Immunotherapy; Laboratory animals; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Manufacturers; Medical research; Mice; Mice, Inbred C57BL; Novels; Oils - chemistry; Papillomavirus E7 Proteins - chemical synthesis; Papillomavirus E7 Proteins - immunology; Papillomavirus Vaccines - immunology; Peptides; Squalene; Synthetic long peptides (SLP); T cells; T-Lymphocytes, Cytotoxic - immunology; TLR4 protein; TLR7 protein; TLR9 protein; Toll-like receptor 9 (TLR9); Toll-Like Receptor 9 - agonists; Toll-Like Receptor 9 - immunology; Toll-like receptors; Tumor Burden; Tumors; Vaccination; Vaccination - methods; Vaccines; Vaccines, Subunit - immunology; Vaccines, Synthetic - immunology; Water; Water - chemistry
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5725-y

Despite considerable efforts at developing therapeutic vaccines for cancer, clinical translation of preclinical successes has been challenging, largely due to the difficulty of inducing strong and sustained cytotoxic T lymphocyte (CTL) responses in patients. Several peptide-based cancer vaccines have failed to show sustainable tumor regression in the clinic, possibly because of a lack of optimization of both the adjuvant and antigen components of the preparations. Here, we aimed to develop and optimize a vaccine format utilizing a synthetic long peptide (SLP) containing the human papilloma virus 16 (HPV16) E7 antigen, with a centrally located defined MHC class I epitope, and evaluate its immunogenicity and efficacy in combination with various adjuvant formulations. E7 SLP was tested alone or in combination with toll-like receptor (TLR)3, TLR4, TLR7/8 and TLR9 agonists and formulated in oil-in-water (o/w) or water-in-oil (w/o) emulsions to determine a vaccine format inducing a robust CD8 T cell response in murine models. Once a lead vaccine format was determined, we examined its ability to inhibit tumor growth in the murine TC-1 model that expresses HPV16 E7 antigen. We identified the TLR9 agonist CpG formulated in a squalene-based o/w emulsion as the most potent adjuvant, inducing the expansion of multifunctional antigen specific CD8 T cells with cytolytic potential. We also demonstrated that SLP E7  + CpG + o/w emulsion vaccine can provide prophylactic and more importantly, therapeutic benefit in the TC-1 murine tumor model. Our results demonstrate that the novel vaccine format E7 SLP + CpG delivered in an o/w emulsion holds potential for the promotion of strong CTL responses and tumor eradication and encourages further development of peptide/adjuvant vaccines in cancer immunotherapy strategies.