<p>Virus–Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development</p>

Abstract

Oncolytic viruses (OVs) are replication competent agents that selectively target cancer cells. After penetrating the tumor cell, viruses replicate and eventually trigger cell lysis, releasing the new viral progeny, which at their turn will attack and kill neighbouring cells. The ability of OVs to self-amplify within the tumor while sparing normal cells can provide several advantages including the capacity to encode and locally produce therapeutic protein payloads, and to prime the host immune system. OVs targeting of cancer cells is mediated by host factors that are differentially expressed between normal tissue and tumors, including viral receptors and internalization factors. In this review article, we will discuss the evolution of oncolytic viruses that have reached the stage of clinical trials, their mechanisms of oncolysis, cellular receptors, strategies for targeting cancers, viral neutralization and developments to bypass virus neutralization.

Emerging Pandemic Diseases: How We Got to COVID-19

“…Other determinants of emerging infectious agents include cell tropism, ability to circumvent innate immune responses, and antigenic immunodominance, among others. Many viruses enter cells via one or more cell receptors ( Figure 4 ) ( Dai et al., 2020 ; Jayawardena et al., 2020 ); some infect different cells via different receptors, while some cell receptors may be entry points for multiple different types of viruses. The situation is extraordinarily complex from the point of view of both virus and host, with a bewildering array of receptors, alternate receptors, and co-receptors and of countless viruses able to utilize them, reflecting that “viruses have deep evolutionary roots in the cellular world” ( Baranowski et al., 2001 ).…”

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

“…There are many cases where anti-viral immunity already exists because most OVs used in anti-cancer therapy are human pathogens that are abundant in the environment. Moreover, repeated OV administration not only induces anti-tumor immunity but also triggers anti-viral immunity [ 82 , 90 ]. Anti-viral immunity can suppress viral replication, facilitate viral clearance, and attenuate anti-tumor activity in immunocompetent patients [ 25 , 82 ].…”

“…For example, neutralizing antibodies against Vaccinia virus target H3L envelope protein and interrupt viral-host fusion [ 91 ]. In the case of adenovirus, pre-existing neutralizing antibodies reduced the anti-tumor efficacy of oncolytic adenovirus [ 90 ]. Furthermore, T-VEC administration is limited to intratumoral injection because of high anti-HSV-1 antibody prevalence in humans [ 90 , 92 ].…”

“…In the case of adenovirus, pre-existing neutralizing antibodies reduced the anti-tumor efficacy of oncolytic adenovirus [ 90 ]. Furthermore, T-VEC administration is limited to intratumoral injection because of high anti-HSV-1 antibody prevalence in humans [ 90 , 92 ]. In addition to pre-existing neutralizing antibodies, anti-viral immunity can also be mediated by the complement system, anti-viral cytokines, and non-specific uptake by off-target organs [ 82 ].…”

“…In addition to pre-existing neutralizing antibodies, anti-viral immunity can also be mediated by the complement system, anti-viral cytokines, and non-specific uptake by off-target organs [ 82 ]. Therefore, to tackle anti-viral immunity, multiple strategies, including genetic manipulation of OV, cytokines, immunomodulators, nanoparticles, and the depletion of neutralizing antibodies, have been explored [ 82 , 83 , 90 ]. On the other hand, there are several conflicting reports suggesting anti-viral immunity could sometimes be beneficial for anti-tumor immunity because anti-viral immunity can recruit anti-tumor immune cells into the TME and reverse the immunosuppressive TME [ 5 , 27 ].…”