The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them
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MINI-REVIEW
The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them Pei-Yang Hu 1 & Xiao-Ming Fan 2 & You-Ni Zhang 1,3,4 & Shi-Bing Wang 3,4 & Wei-Jie Wan 5 & Hong-Ying Pan 6 & Xiao-Zhou Mou 3,4 Received: 22 June 2020 / Revised: 22 June 2020 / Accepted: 30 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. Key points • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized. Keywords Oncolytic virus . Immunotherapy . Oncolytic virus delivery systems . Viral-mediated anti-tumor response . Cancer
Introduction Oncolytic viruses (OVs) are a class of viruses which infect and kill cancer cells (Zheng et al. 2019). They were first identified at the beginning of the nineteenth century when early case reports showed regression of cancers during certain viral
infections. However, this therapeutic approach was soon dismissed due to its inefficacy as host immune systems eliminated the viral infection before it could impact the tumor growth (Kelly and Russell 2007). Advancements in molecular biology and genetic manipulation, which allow for the generation of more potent and tumor-specific viruses, have brought
Pei-Yang Hu and Xiao-Ming Fan contributed equally to this work. * Hong-Ying Pan [email protected]
3
Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310014, China
4
Clinical Research Institute, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310014, China
5
Shandong Xiandai University, Jinan 250104, China
6
Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medical College), Hangzhou 310014, China
* Xiao-
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