Oncolytic polio virotherapy of cancer

Abstract

Recently, the century-old idea of targeting cancer with viruses (‘oncolytic viruses’) has come of age, with promise documented in early-stage and several late-stage clinical trials in a variety of cancers. While originally prized for their direct tumor cytotoxicity (‘oncolytic virotherapy’), recently, the pro-inflammatory and immunogenic effects of viral tumor infection (‘oncolytic immunotherapy’) have come into focus. Indeed, a capacity for eliciting broad, sustained anti-neoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal pro-inflammatory stimulation and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Due to fundamentally different relationships with their hosts (malignant or not), diverse replication strategies and distinct modes of tumor cytotoxicity/ killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, we highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO, and their implications for oncolytic immunotherapy in the clinic.

Strategic Combinations: The Future of Oncolytic Virotherapy with Reovirus

“…Among the leading viral candidates are the modified or natural form of herpes simplex (1), poliovirus (2), measles (3), poxvirus (4), vaccinia (5), vesicular stomatitis (6), and reovirus. Reovirus is one of the leading OVs in therapeutic development (REOLYSIN, Oncolytics Biotech Inc.) and is in phase I, phase II, and phase III clinical trials internationally.…”

Comment on: Glioblastoma multiforme outcomes of 107 patients treated in two local institutions

“…What the authors do not mention, however, is the potential effectiveness of employing viral, immunological and molecular treatment modalities. (2,3) Oncolytic viruses have recently shown great promise in the treatment of GBM, (3,4) an important fi nding for such cancers that have little or no potential for survival. Apart from GBM, there are other cancers such as melanoma that also do not benefi t from classical treatments.…”

“…Apart from GBM, there are other cancers such as melanoma that also do not benefi t from classical treatments. (4) Innovative therapies employing oncolytic, immunological or molecular properties do not represent a 'magic bullet' and require specifi c characteristics when targeting certain cancers. There remain problems with tropism, unique cell properties and strategies to maximise the optimal effi ciency for the treatment.…”

“…Specifi cally, the application of a modifi ed polio virus has been shown to be effective in the treatment of GBM, with cases of possible remission. (2,4) This viral treatment appears to involve actions specifi c to this type of tumour and recruitment of the host immunological system.…”

“…(2,4) Hence, it might be better to approach treatment of GBM with a biological mechanism in the future, rather than applying traditional modalities (e.g. chemotherapy, radiation or surgery).…”