Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy
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REVIEW
Open Access
Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy Bin Zhang and Ping Cheng*
Abstract As a promising therapeutic strategy, oncolytic virotherapy has shown potent anticancer efficacy in numerous preclinical and clinical trials. Oncolytic viruses have the capacity for conditional-replication within carcinoma cells leading to cell death via multiple mechanisms, including direct lysis of neoplasms, induction of immunogenic cell death, and elicitation of innate and adaptive immunity. In addition, these viruses can be engineered to express cytokines or chemokines to alter tumor microenvironments. Combination of oncolytic virotherapy with other antitumor therapeutic modalities, such as chemotherapy and radiation therapy as well as cancer immunotherapy can be used to target a wider range of tumors and promote therapeutic efficacy. In this review, we outline the basic biological characteristics of oncolytic viruses and the underlying mechanisms that support their use as promising antitumor drugs. We also describe the enhanced efficacy attributed to virotherapy combined with other drugs for the treatment of cancer. Keywords: Oncolytic virus, Oncolysis, Tumor tropism, Innate and adaptive immunity, Immunogenic cell death, Combination therapy, Antitumor
Introduction Oncolytic virotherapy is an immunotherapeutic modality that utilizes naturally or genetically modified oncolytic viruses (OVs) to propagate in and selectively destroy carcinoma cells combined with a reduced capacity for infection and oncolysis of normal tissues and cells [1]. The unique characteristics of OVs in treating tumors have increased interest in oncolytic virotherapy research, with pre-clinical and clinical evaluation of a host of oncolytic virotherapies, including vesicular stomatitis virus (VSV) [2], adenovirus [3], vaccinia virus [4], and measles virus [5]. To date, only Talimogene laherparepvec (T-VEC), which is an attenuated herpes simplex virus type 1 (HSV-1) developed for the treatment of melanoma, has * Correspondence: [email protected] State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, 17 People’s South Road, Chengdu 610041, PR China
been approved by the Food and Drug Administration. In this oncolytic agent, the ICP34.5 and ICP47 regions have been deleted and granulocyte-macrophage colonystimulating factor (GM-CSF) has been inserted [6]. For most viruses, a nucleic acid core composed of DNA or RNA and protein capsid (a nucleic coat) are integral to infection and proliferation, and, in some viruses, the lipid-rich envelope coating the capsid protein is required to promote viral attachment and entry into host cells. Oncolytic DNA viruses have high genome stability and large transgenes can be inserted into the viral vectors without impairing viral infection and replication function [7]. In contrast, most RNA viruses have limited genome packing capacity, and yet, are less likely to cause insertion mutatio
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