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Oncoimmunology. 2018 Mar 27;7(7):e1445459. doi: 10.1080/2162402X.2018.1445459. eCollection 2018.

Transforming the prostatic tumor microenvironment with oncolytic virotherapy.

Author information

1
McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
2
Turnstone Biologics, Ottawa, Canada.
3
Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Canada.
4
McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Canada.
5
Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
6
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Canada.
7
Stojdl Lab, CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Canada.
8
Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada.
9
Department of Surgery, The Ottawa Hospital, Ottawa, Canada.
10
Department of Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Canada.
11
Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
12
Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Canada.

Abstract

Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa.

KEYWORDS:

MG1-Maraba; STEAP; prostatic carcinoma; tumor microenvironment; vaccination

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