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Vaccine v.36 no.16, 2018년, pp.2181 - 2192   SCI SCIE SCOPUS
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

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

Atherton, Matthew J. (McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada ) ; Stephenson, Kyle B. (Turnstone Biologics, Ottawa, Canada ) ; Nikota, Jake K. (Turnstone Biologics, Ottawa, Canada ) ; Hu, Qian N. (Turnstone Biologics, Ottawa, Canada ) ; Nguyen, Andrew (McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada ) ; Wan, Yonghong (McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada ) ; Lichty, Brian D. (McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada ) ;
  • 초록  

    Abstract 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. Highlights 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.


  • 주제어

    Oncolytic vaccination .   HPV-associated cancer .   Peptide vaccine design .   Cancer immunotherapy .   MG1 Maraba.  

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