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Open AccessArticle

Overcoming Tumor Resistance to Oncolyticvaccinia Virus with Anti-PD-1-Based Combination Therapy by Inducing Antitumor Immunity in the Tumor Microenvironment

1
BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, Korea
2
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea
3
Biomedical Sciences, School of Medicine, Pusan National University, Yangsan 50612, Korea
4
Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan 49241, Korea
*
Authors to whom correspondence should be addressed.
Vaccines 2020, 8(2), 321; https://doi.org/10.3390/vaccines8020321
Received: 19 May 2020 / Revised: 14 June 2020 / Accepted: 16 June 2020 / Published: 19 June 2020
(This article belongs to the Special Issue Cancer Vaccine)
The tumor microenvironment (TME) comprises different types of immune cells, which limit the therapeutic efficacy of most drugs. Although oncolytic virotherapy (OVT) boosts antitumor immunity via enhanced infiltration of tumor-infiltrated lymphocytes (TILs), immune checkpoints on the surface of tumors and TILs protect tumor cells from TIL recognition and apoptosis. OVT and immune checkpoint blockade (ICB)-based combination therapy might overcome this issue. Therefore, combination immunotherapies to modify the immunosuppressive nature of TME and block immune checkpoints of immune cells and tumors are considered. In this study, cancer-favoring oncolytic vaccinia virus (CVV) and anti–programmed cell death protein-1 (anti-PD-1) were used to treat mouse colorectal cancer. Weekly-based intratumoral CVV and intraperitoneal anti-PD-1 injections were performed on Balb/c mice with subcutaneous CT26 tumors. Tumor volume, survival curve, and immunohistochemistry-based analysis demonstrated the benefit of co-treatment, especially simultaneous treatment with CVV and anti-PD-1. Infiltration of CD8+PD-1+ T-cells showed correlation with these results. Splenocytes enumeration also suggested CD4+ and CD8+ T-cell upregulation. In addition, upregulated CD8, PD-1, and CD86 messenger RNA expression was observed in this combination therapy. Therefore, CVV+anti-PD-1 combination therapy induces antitumor immunity in the TME, overcoming the rigidity and resistance of the TME in refractory cancers. View Full-Text
Keywords: oncolytic virotherapy; immunotherapy; tumor microenvironment; vaccinia virus; immune checkpoints oncolytic virotherapy; immunotherapy; tumor microenvironment; vaccinia virus; immune checkpoints
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Yoo, S.Y.; Badrinath, N.; Jeong, S.-N.; Woo, H.Y.; Heo, J. Overcoming Tumor Resistance to Oncolyticvaccinia Virus with Anti-PD-1-Based Combination Therapy by Inducing Antitumor Immunity in the Tumor Microenvironment. Vaccines 2020, 8, 321.

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