Cancer immunotherapy and the emergence of immune checkpoint inhibitors have markedly changed the treatment paradigm for many cancers. They function to disrupt cancer cell evasion of the immune response and activate sustained anti-tumor immunity. Oncolytic viruses have also emerged as an additional therapeutic agent for cancer treatment. These viruses are designed to target and kill tumor cells while leaving the normal cells unharmed. As part of this process, oncolytic virus infection stimulates anti-cancer immune responses that augment the efficacy of checkpoint inhibition. These viruses have the capability of transforming a "cold" tumor microenvironment with few immune effector cells into a "hot" environment with increased immune cell and cytokine infiltration. For this reason, there are multiple ongoing clinical trials that combine oncolytic virotherapy and immune checkpoint inhibitors. This review will detail the key oncolytic viruses in preclinical and clinical studies and highlight the results of their testing with checkpoint inhibitors.
Because therapeutic cancer vaccines can, in theory, eliminate tumor cells specifically with relatively low toxicity, they have long been considered for application in repressing cancer progression. Traditional cancer vaccines containing a single or a few discrete tumor epitopes have failed in the clinic, possibly due to challenges in epitope selection, target downregulation, cancer cell heterogeneity, tumor microenvironment immunosuppression, or a lack of vaccine immunogenicity. Whole cancer cell or cancer membrane vaccines, which provide a rich source of antigens, are emerging as viable alternatives.
Immunotherapy has been advanced through multiple approaches, including immunogenic cytokines, monoclonal antibodies, therapeutic vaccinations, adoptive cell transfer, stem cell transplantation, and oncolytic viruses. This review analyses various strategies in genomics, transcriptomics, single-cell techniques, computational analysis, big data, and imaging technologies for the identification of tumour microbiota and microenvironments. Immunotherapy is becoming acknowledged as a feasible cancer treatment method, facilitating innovative cancer medicines and personalized medicine techniques.
The sensitivity of human glioblastoma cells to virus-mediated oncolysis was investigated on five patient-derived cell lines. Primary glioblastoma cells (Gbl13n, Gbl16n, Gbl17n, Gbl25n, and Gbl27n) were infected with tenfold serial dilutions of the Leningrad-3 strain of the mumps virus, and virus reproduction and cytotoxicity were monitored for 96-120 h. Immortalized human non-tumor NKE cells were used as controls to determine the virus specificity.
Viral products keep gaining importance in multiple therapeutic fields. Considering the scale and production slot limitations, optimizing the outcome of every manufacturing batch is essential to minimize costs and make this therapeutic modality broadly available to patients. Most manufacturing processes for oncolytic viruses currently in clinical studies are based on a batch process.
Viruses can be designed to be tools and carrier vehicles for intratumoural immunotherapy. Their nanometre-scale size and shape allow for functionalization with or encapsulation of medical cargoes and tissue-specific ligands. Importantly, immunotherapies may particularly benefit from the inherent immunomodulatory properties of viruses.
