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From Vaccine Vector to Oncomodulation: Understanding the Complex Interplay between CMV and Cancer

Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 62;
Received: 31 May 2019 / Revised: 2 July 2019 / Accepted: 4 July 2019 / Published: 9 July 2019
(This article belongs to the Special Issue Cytomegalovirus Infection and Vaccine Development)
Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8+ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the efficacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much less is known and only very early studies in mice have been conducted. To develop CMV-based cancer vaccines further, it will be critical to better understand the complex interaction of CMV and cancer. An array of evidence suggests that naturally-acquired human (H)CMV can be detected in cancers, and it has been proposed that HCMV may promote tumor growth. This would obviously be a concern for any therapeutic cancer vaccines. In experimental models, CMV has been shown to play both positive and negative roles in tumor progression, depending on the model studied. However, the mechanisms are still largely unknown. Thus, more studies assessing the interaction of CMV with the tumor microenvironment are needed. This review will summarize the existing literature and major open questions about CMV-based vaccines for cancer, and discuss our hypothesis that the balance between pro-tumor and anti-tumor effects driven by CMV depends on the location and the activity of the virus in the lesion. View Full-Text
Keywords: cytomegalovirus; cancer vaccines; oncomodulation; anti-tumor immunity cytomegalovirus; cancer vaccines; oncomodulation; anti-tumor immunity
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Wilski, N.A.; Snyder, C.M. From Vaccine Vector to Oncomodulation: Understanding the Complex Interplay between CMV and Cancer. Vaccines 2019, 7, 62.

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