Intelligent Design: Combination Therapy With Oncolytic Viruses

Abstract

Metastatic cancer remains an incurable disease in the majority of cases and thus novel treatment strategies such as oncolytic virotherapy are rapidly advancing toward clinical use. In order to be successful, it is likely that some type of combination therapy will be necessary to have a meaningful impact on this disease. Although it may be tempting to simply combine an oncolytic virus with the existing standard radiation or chemotherapeutics, the long-term goal of such treatments must be to have a rational, potentially synergistic combination strategy that can be safely and easily used in the clinical setting. The combination of oncolytic virotherapy with existing radiotherapy and chemotherapy modalities is reviewed along with novel biologic therapies including immunotherapies, in order to help investigators make intelligent decisions during the clinical development of these products.

A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer

“…Combination therapy with an oncolytic virus and conventional chemotherapy has been reported to be a promising treatment strategy for advanced cancers. [24][25][26] We plan to administer six injections of HF10 for nonresectable pancreatic cancers using an endoscopic ultrasound. The current mainstream methods for cancer treatment are novel biological therapeutics, and oncolytic viruses are one type of biological therapeutic that appear to have a wide spectrum of anticancer activity with minimal human toxicity.…”

GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution

“…To evaluate the intratumoral efficacy of the fusogenic adenovirus ICOVIR16, mice bearing established SkMel-28 tumors (130 mm 3 ) received a single intratumoral injection of PBS or 1 Â 10 9 viral particles of each virus (n ¼ 10). To evaluate systemic efficacy, subcutaneous SkMel-28 melanoma or NP18 pancreatic tumors were established by injection of 5 Â 10 6 cells into the flanks of 6-week-old male Balb/C nu/nu mice.…”

“…1 The feasibility and safety of oncolytic adenoviruses in human patients have been demonstrated in clinical trials with multiple modes of delivery, and the combination with standard chemotherapy or radiotherapy has the potential to further increase the antitumor activity of oncolytic adenoviruses. 2,3 However, a significant therapeutic effect has not been clearly demonstrated to date. Therefore, improvements in the efficacy of oncolytic adenoviruses are required to obtain clear benefits in cancer patients.…”

Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing

“…While promising early-and late-phase clinical trials employing OVs to treat cancers continue to generate great enthusiasm, heterogeneity in clinical response remains a challenge [2][3][4] . To this end, it has been long recognized that improvements to therapeutic efficacy either through viral engineering or through combination therapies will be critical to the success of these platforms 2,5 .…”