Current strategies to circumvent the antiviral immunity to optimize cancer virotherapy

Abstract

Cancer virotherapy is a paradigm-shifting treatment modality based on virus-mediated oncolysis and subsequent antitumor immune responses. Clinical trials of currently available virotherapies showed that robust antitumor immunity characterizes the remarkable and long-term responses observed in a subset of patients. These data suggest that future therapies should incorporate strategies to maximize the immunotherapeutic potential of oncolytic viruses. In this review, we highlight the recent evidence that the antiviral immunity of the patients may limit the immunotherapeutic potential of oncolytic viruses and summarize the most relevant approaches to strategically redirect the immune response away from the viruses and toward tumors to heighten the clinical impact of viro-immunotherapy platforms.

Agent-based computational modeling of glioblastoma predicts that stromal density is central to oncolytic virus efficacy

“…We chose these four parameters as they can be modulated when an OV is generated (through modification or encapsulation) or vary greatly between OV derivatives. Viral diffusion can be increased through the modification of the TME ( Goradel et al., 2020 ), viral decay by the immune system can be decreased through encapsulation with shields ( Shin et al., 2021 ), and viral infectivity and burst size can vary greatly between oncolytic derivatives ( Macedo et al., 2020 ) and can also be modified through modifying viral receptor attachment ( Cattaneo et al., 2008 ).…”

“…Co-administration of OVs with junction opening peptides increases the spread of virus throughout the tumor by degrading the tight junctions that exist between cells ( Yumul et al., 2016 ). Similarly, there are many strategies to circumvent antiviral immunity ( Shin et al., 2021 ), and hence clearance of an OV. OVs can be shielded from the humoral immune responses through encapsulation in protective coatings and carriers.…”

Recombinant Viral Vectors for Therapeutic Programming of Tumour Microenvironment: Advantages and Limitations

“…It seems that there is a need to work out a reliable test protocol for personalised tumour infectivity evaluation for main virus vectors applied in clinics, as this is the crucial point for virus therapy efficacy. A second important issue that has to be assessed is the possible pre-existing immunity against the vector, which could influence the outcome of therapy significantly [ 16 ].…”

Remission of liquid tumors and SARS-CoV-2 infection: A literature review

“…36,37 The use of transgenes to activate the immune system during oncolytic virus infection and the utilization of cell vehicles 38 for the delivery of viruses to tumors are areas of research and are reviewed elsewhere. [39][40][41]…”