Transforming the prostatic tumor microenvironment with oncolytic virotherapy.

Autor: Atherton MJ; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada., Stephenson KB; Turnstone Biologics, Ottawa, Canada., Tzelepis F; Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Canada., Bakhshinyan D; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Canada.; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Canada., Nikota JK; Turnstone Biologics, Ottawa, Canada., Son HH; Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Canada., Jirovec A; Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Canada., Lefebvre C; Stojdl Lab, CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Canada., Dvorkin-Gheva A; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada., Ashkar AA; 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., Stojdl DF; Turnstone Biologics, Ottawa, Canada.; Stojdl Lab, CHEO Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Canada., Belanger EC; Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada., Breau RH; Department of Surgery, The Ottawa Hospital, Ottawa, Canada., Bell JC; Turnstone Biologics, Ottawa, Canada.; Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Canada., Saad F; Department of Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Canada., Singh SK; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Canada.; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Canada.; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Canada.; Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Canada., Diallo JS; Centre for Cancer Therapeutics, The Ottawa Hospital Research Institute, Ottawa, Canada.; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Canada., Lichty BD; McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.; Turnstone Biologics, Ottawa, Canada.
Jazyk: angličtina
Zdroj: Oncoimmunology [Oncoimmunology] 2018 Mar 27; Vol. 7 (7), pp. e1445459. Date of Electronic Publication: 2018 Mar 27 (Print Publication: 2018).
DOI: 10.1080/2162402X.2018.1445459
Abstrakt: 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.
Databáze: MEDLINE