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      Combination Immunotherapy Using Oncolytic Virus for the Treatment of Advanced Solid Tumors

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          Abstract

          Oncolytic virus (OV) is a new therapeutic strategy for cancer treatment. OVs can selectively infect and destroy cancer cells, and therefore act as an in situ cancer vaccine by releasing tumor-specific antigens. Moreover, they can remodel the tumor microenvironment toward a T cell-inflamed phenotype by stimulating widespread host immune responses against the tumor. Recent evidence suggests several possible applications of OVs against cancer, especially in combination with immune checkpoint inhibitors. In this review, we describe the molecular mechanisms of oncolytic virotherapy and OV-induced immune responses, provide a brief summary of recent preclinical and clinical updates on this rapidly evolving field, and discuss a combinational strategy that is able to overcome the limitations of OV-based monotherapy.

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          PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

          Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.
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            Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

            Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules. Insights into the underlying biological mechanisms and functions of these molecules have, however, lagged significantly behind. Such understanding will be essential for the rational design of next-generation immunotherapies. Here, we review the current state of our understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, and highlight conceptual gaps in knowledge.Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1069-86. ©2018 AACR.
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              Immune checkpoint inhibitors: recent progress and potential biomarkers

              Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                19 October 2020
                October 2020
                : 21
                : 20
                : 7743
                Affiliations
                [1 ]Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea; cmoh@ 123456gist.ac.kr
                [2 ]Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13497, Korea
                Author notes
                [* ]Correspondence: minidoctor@ 123456cha.ac.kr (H.J.C.); chan@ 123456cha.ac.kr (C.K.)
                Author information
                https://orcid.org/0000-0001-9780-6155
                Article
                ijms-21-07743
                10.3390/ijms21207743
                7589893
                33086754
                5eb55ae5-4536-4aab-b789-9360d8469ccc
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 September 2020
                : 16 October 2020
                Categories
                Review

                Molecular biology
                oncolytic virus,combination immunotherapy,immune checkpoint inhibitor,tumor microenvironment

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