Abstract

Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination. Classical strategies include ex vivo-loaded immune cells, RNA- or DNA-based vaccines and tumour cell lysates. Recent oncolytic virus development has resulted in a surge of novel viruses engineered to induce powerful tumour-specific immune responses. In addition to their use as cancer vaccines, oncolytic viruses have the added benefit of being directly cytolytic to cancer cells and thus promote antigen recognition within a highly immune-stimulating tumour microenvironment. While oncolytic viruses are perfectly equipped for efficient immunization, this complicates their use upon previous exposure. Indeed, the host’s anti-viral counter-attacks often impair multiple-dosing regimens. In this review we will focus on the use of oncolytic viruses for anti-tumour vaccination. We will explore different strategies as well as ways to circumvent some of their limitations.

Highlights

  • The field of cancer therapy has seen significant progression within recent years and as a result, has directly improved the outlook for cancer patients

  • The exciting clinical results obtained from human papillomavirus (HPV) and HBV immunization emphasize the potential of cancer vaccines; the majority of cancers are diagnosed only once well established

  • Results from a phase I clinical trial using intravenously administered oncolytic reovirus for the treatment of advanced cancer patients showed that CD4 T cell, CD8 T cell and NK cell numbers were increased in 47.6%, 33%, and 28.6% of patients, respectively [68]

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Summary

Introduction

The field of cancer therapy has seen significant progression within recent years and as a result, has directly improved the outlook for cancer patients. Oncolytic viruses (OV) are exciting immunotherapeutic candidates as they are a novel and versatile treatment option capable of inducing anti-tumour immunity [7,8,9,10] In recent years, they have been further engineered for anti-cancer vaccination and this strategy is currently being tested clinically. The exciting clinical results obtained from HPV and HBV immunization emphasize the potential of cancer vaccines; the majority of cancers are diagnosed only once well established This further supports the need for effective therapeutic vaccines for patients unable to be treated with preventive immunization. During the negative selection step of thymic education, autoreactive T cells are depleted to prevent autoimmunity and only a limited number can be found in the periphery While this clearance step is crucial to prevent self-destruction, it impairs tumour recognition, as most cancer antigens are aberrantly expressed or modified self-molecules. Breaking this tolerance is one of the main challenges of anti-tumour vaccination and will be discussed further

Therapeutic Anti-Cancer Vaccines
A Viral Strategy
Clinical Evidence of OV-Induced Immunity
Coating Viruses
Non-Replicating Viruses
Infected Cell Vaccines
10. The Barriers to Viral Vaccination Strategies
Findings
11. Conclusions
Full Text
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