Mechanisms of measles virus oncolytic immunotherapy. 2020

Gemma Pidelaserra-Martí, and Christine E Engeland
Research Group Mechanisms of Oncolytic Immunotherapy, Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University and Helmholtz International Graduate School for Cancer Research, DKFZ, Heidelberg, Germany. Electronic address: gemma.pidelaserramarti@nct-heidelberg.de.

The study of measles virus (MeV) as a cancer immunotherapeutic was prompted by clinical observations of leukemia and lymphoma regressions in patients following measles virus infection in the 1970s and 1980s. Since then, numerous preclinical studies have confirmed the oncolytic activity of MeV vaccine strains as well as their potential to promote long-lasting tumor-specific immune responses. Early clinical data indicate that some of these effects may translate to the treatment of cancer patients. In this review, we provide a structured summary of current evidence for the anti-tumor immune activity of oncolytic MeV. We start with an overview of MeV oncolysis and MeV-induced immunogenic cell death. Next, we relate findings on MeV-mediated activation of antigen-presenting cells, T cell priming and effector mechanisms to the cancer immunity cycle. We discuss additional factors in the tumor microenvironment which are modulated by MeV treatment as well as the role of anti-viral immunity. Based on these findings, we highlight avenues for rational enhancement of oncolytic MeV immunotherapy by vector engineering. We further point to advantages and drawbacks of experimental models and propose areas warranting promising research. Lastly, we review the available immunomonitoring data from several Phase I clinical trials. While this review presents data for MeV, the concepts and principles introduced herein apply to other oncolytic viruses, providing a framework to assess novel cancer immunotherapies.

UI MeSH Term Description Entries
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D008458 Measles Vaccine A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed) Vaccine, Measles
D008459 Measles virus The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children. Edmonston virus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D050130 Oncolytic Virotherapy Use of attenuated VIRUSES as ANTINEOPLASTIC AGENTS to selectively kill CANCER cells. Oncolytic Virus Therapy,Virotherapy, Oncolytic,Oncolytic Virotherapies,Oncolytic Virus Therapies,Therapies, Oncolytic Virus,Therapy, Oncolytic Virus,Virotherapies, Oncolytic,Virus Therapies, Oncolytic,Virus Therapy, Oncolytic
D050504 Oncolytic Viruses Tumor-selective, replication competent VIRUSES that have antineoplastic effects. This is achieved by producing cytotoxicity-enhancing proteins and/or eliciting an antitumor immune response. They are genetically engineered so that they can replicate in CANCER cells but not in normal cells, and are used in ONCOLYTIC VIROTHERAPY. Oncolytic Virus,Virus, Oncolytic,Viruses, Oncolytic

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