Preclinical development of peptide vaccination combined with oncolytic MG1-E6E7 for HPV-associated cancer

• Published in: Vaccine Vol. 36; no. 16; pp. 2181 - 2192
• Main Authors: Atherton, Matthew J., Stephenson, Kyle B., Nikota, Jake K., Hu, Qian N., Nguyen, Andrew, Wan, Yonghong, Lichty, Brian D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 12.04.2018; Elsevier Limited
• Subjects: Adenoviruses; Antigens; Cancer; Cancer immunotherapy; Cancer therapies; CD8 antigen; Cervical cancer; Customization; Design; Epitope mapping; Global health; HPV-associated cancer; Human papillomavirus; Immune response; Immunity; Immunotherapy; Infections; Lymphocytes; Lymphocytes T; Metastasis; MG1 Maraba; Mice; Oncolysis; Oncolytic vaccination; Peptide vaccine design; Peptides; Proteins; Tumors; Vaccines; Viruses; Ad; IL1β; MOI; OV; Oncolytic vaccination; Cancer immunotherapy; PBMC; TME; HPV; MG1 Maraba; IFN-γ; TNF-α; TAA; MG1; SLP; Peptide vaccine design; HPV-associated cancer
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.02.070

•MG1-E6E7 is a multifunctional oncolytic with numerous mechanisms of activity.•MG1-E6E7 boosts responses against multiple CD8+ HPV epitopes.•Epitope mapping enabled the rational design of synthetic long peptide vaccines.•SLPs boosted by MG1-E6E7 completely clear 60% of large HPV positive tumours in mice. Human papilloma virus (HPV)-associated cancer is a significant global health burden and despite the presence of viral transforming antigens within neoplastic cells, therapeutic vaccinations are ineffective for advanced disease. HPV positive TC1 cells are susceptible to viral oncolysis by MG1-E6E7, a custom designed oncolytic Maraba virus. Epitope mapping of mice vaccinated with MG1-E6E7 enabled the rational design of synthetic long peptide (SLP) vaccines against HPV16 and HPV18 antigens. SLPs were able to induce specific CD8+ immune responses and the magnitude of these responses significantly increased when boosted by MG1-E6E7. Logically designed vaccination induced multi-functional CD8+ T cells and provided complete sterilising immunity of mice challenged with TC1 cells. In mice bearing large HPV-positive tumours, SLP vaccination combined with MG1-E6E7 was able to clear tumours in 60% of mice and these mice were completely protected against a long term aggressive re-challenge with the TC1 tumour model. Combining conventional SLPs with the multi-functional oncolytic MG1-E6E7 represents a promising approach against advanced HPV positive neoplasia.