Integrating oncolytic viruses in combination cancer immunotherapy

Abstract

Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments. Oncolytic viruses can also utilize established tumours as an in situ source of neoantigen vaccination through cross-presentation, resulting in regression of distant, uninfected tumours. These features make oncolytic viruses attractive agents for combination strategies to optimize cancer immunotherapy.

Enhancement of Oncolytic Activity of oHSV Expressing IL-12 and Anti PD-1 Antibody by Concurrent Administration of Exosomes Carrying CTLA-4 miRNA

“…Success of the checkpoint inhibitors in treatment of cancer hinges on the concurrent presence of an activated immune response to the cancer cells [20,21]. The combination of the two approaches, namely the use of oncolytic viruses to trigger innate immunity to the cancer cells concurrently with systemic administration of checkpoint inhibitors proved to be much more effective than either approach alone [22][23][24][25][26]. The disadvantage of systemic administration of checkpoint inhibitors is the rare misdirection of the activated immune response resulting in devastating damage to healthy organs [27].…”

Trial watch: Peptide-based vaccines in anticancer therapy

“…267-269 In line with this notion, the vast majority of peptide-based vaccines tested in the clinic so far mediated limited, if any, therapeutic activity, despite being able to elicit tumor-targeting immune responses, at least to some degree. 118 The field is therefore moving along three non-mutually exclusive directions: (1) combining peptide-based vaccination with additional forms of (immuno)therapy, with the specific aim of reverting immunosuppression and enabling therapeutically relevant immune responses, 270-272 (2) targeting private antigenic epitopes that originate from mutations affecting only malignant cells (or sub-populations thereof), with PPV, 167,272-275 and (3) identifying specific patient populations that may obtain clinical benefit from the use of peptide-based vaccination. 174,254 Although the feasibility of PPV on a large scale remains unclear, we surmise combining some variants of peptide-based vaccination with potent immunostimulatory agents including immune checkpoint blockers and oncolytic viruses may be the key to unlock the true potential of this hitherto unrealized therapeutic modality.…”

Development of oncolytic virotherapy: from genetic modification to combination therapy

“…The tumor tropism of OVs is an important feature to ensure that they selectively replicate in and specifically kill tumor cells [79]. Wild-type OVs generally depend on tumorspecific cellular receptors or abnormal intracellular pathways and products to enter and selectively replicate in tumor cells and therefore can be optimized through genetic modifications to enhance their tumor targeting.…”

“…Through genetic engineering, an arginine-glycine-aspartic acid (RGD) motif was inserted into the fiber knob domain of Ad5 to generate a newly modified virus, which no longer depends on CAR to enter tumor cells and instead relies on integrins that are highly expressed on tumor cells, to enter tumor cells [82]. Other studies inserted the fiber knob domain derived from adenovirus type 3 (Ad3) into the backbone of Ad5 (also named serotype switching) to allow its entrance to the tumor cells by utilizing the highly expressed Ad3 receptor (desmoglein 2 as the primary receptor) on tumor cells to enter the tumor cells [79]. A similar modification involves inserting the fiber knob domain of adenovirus type 35 (Ad35) into the backbone of Ad5, allowing the OVs to utilize the Ad35 receptor (CD46 as the primary receptor) to enter tumor cells [81].…”

“…However, some shortcomings or problems still confound the full use of OVT. For example, the small genomic capacities of some OVs, such as coxsackievirus and reovirus, limit their ability to accommodate large foreign genes that can optimize their antitumor efficacy [79]. Genetic modification by deleting virulence genes to improve the safety of OVs also reduces the antitumor efficacy of OVs [241].…”