Taking a Stab at Cancer; Oncolytic Virus-Mediated Anti-Cancer Vaccination Strategies

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.

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

“…The expression of CTAs in adult human organs is limited to immune‐privileged sites, e.g. the testis and, for some CTAs, occasionally the placenta and the brain . In this study, we have shown that PRAME, which is a highly immunogenic CTA, is expressed in 83% of SDCs, but in none of the background tissues, e.g.…”

“…the testis and, for some CTAs, occasionally the placenta and the brain. 21,51 In this study, we have shown that PRAME, which is a highly immunogenic CTA, is expressed in 83% of SDCs, but in none of the background tissues, e.g. salivary glands, ICs, and stromal cells.…”

“…The presence of the MHC I–tumour antigen complex on the tumour cell surface in response to tumour antigen‐specific cytotoxic T cells is an important step of T‐cell‐mediated adaptive immune response . Down‐regulation of MHC I is frequently observed in many cancer types, and is a key mechanism of cancer immune evasion, contributing to the disappointing clinical results of T‐cell‐based immunotherapy and tumour antigen‐specific cancer vaccination . Complete loss or heterogeneous expression of MHC I has been reported in 19–66% of HNSCCs, and has been associated with adverse clinical outcomes .…”

“…CTAs are common tumour antigens that are specifically expressed in many solid cancer types, including HNSCC and salivary gland carcinoma. 23,[51][52][53][54][55][56] The expression of CTAs in adult human organs is limited to immune-privileged sites, e.g. the testis and, for some CTAs, occasionally the placenta and the brain.…”

“…28 Down-regulation of MHC I is frequently observed in many cancer types, and is a key mechanism of cancer immune evasion, contributing to the disappointing clinical results of T-cell-based immunotherapy and tumour antigen-specific cancer vaccination. 28,51 Complete loss or heterogeneous expression of MHC I has been reported in 19-66% of HNSCCs, [17][18][19][20]28 and has been associated with adverse clinical outcomes. 17,19,58 MHC I expression in SDC and its prognostic significance have not yet been well studied.…”