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

Autor: Atherton MJ; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada., Stephenson KB; Turnstone Biologics, Ottawa, Canada., Nikota JK; Turnstone Biologics, Ottawa, Canada., Hu QN; Turnstone Biologics, Ottawa, Canada., Nguyen A; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada., Wan Y; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada., Lichty BD; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada; Turnstone Biologics, Ottawa, Canada. Electronic address: lichtyb@mcmaster.ca.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2018 Apr 12; Vol. 36 (16), pp. 2181-2192. Date of Electronic Publication: 2018 Mar 12.
DOI: 10.1016/j.vaccine.2018.02.070
Abstrakt: 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.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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