Viruses in cancer therapy - from benchwarmers to quarterbacks

Abstract

A recent clinical trial of a virotherapy approach, consisting of an engineered poliovirus, has provided evidence of apparently durable responses in patients with recurrent glioblastoma. The results of this trial and others indicate that virotherapy might be an effective tool in anticancer immunotherapy. Yet, caution must be exercised until appropriately powered randomized clinical trials truly show efficacy.

Fig. 1 |. The current hypothesis for anticancer mechanisms of oncolytic virotherapy.

Initial viral infection of tumour cells leads to some degree of direct cytotoxicity, with cell lysis enabling the spread of replicative viruses to surrounding cells. Consequently, the inflammatory response to the infection alters the microenvironment of the tumour from immunologically ‘cold’ to ‘hot’ owing to recruitment and activation of innate and adaptive immune cells capable of mediating anticancer responses. The US National Library of Medicine ClinicalTrials.gov database lists several open clinical trials of different virotherapies for glioblastoma, such as studies using the modified poliovirus PVSRIPO (NCT02986178 and NCT03043391), herpes simplex viruses (NCT02457845, NCT03152318, and NCT02062827), adenoviruses (NCT02798406, NCT03178032, NCT03072134, NCT01811992, NCT02026271, and NCT03576612), retroviruses (NCT02414165), reoviruses (NCT02444546), and vaccinia viruses (NCT03294486). TCR, T cell receptor.