Virotherapy represents the experimental use of oncolytic viruses to treat cancer. This type of treatment provides a plethora of potential advantages in comparison to conventional cancer therapies, such as selectiveness for tumor cells, initiation of a potent antitumor response and cytotoxicity for surviving cancer and stromal cells.
Intratumoral injection was a way to administer oncolytic viruses in a majority of clinical trials that were performed thus far; regional or intravenous delivery was examined in just a fraction of studies. Albeit overall efficacy against tumors has been limited, clinical experience has shown a favorable safety and toxicity profile, as well as a number of tumor responses.
Products used in virotherapy
A nonpathogenic, oncolytic ECHO-7 virus adapted for melanoma that has not been genetically modified was the first approved virotherapy product. Registered in Latvia in 2004 (under a name Rigvir), this virus represents a specific immunotherapy approach for patients with melanoma, and can result in a 4.39-6.57-fold lower mortality when compared to a group under observation only.
Talimogene laherparepvec, formerly named OncoVEX, is a modified injectable oncolytic herpes simplex virus that codes for granulocyte/macrophage colony stimulating factor (GM-CSF). Akin to Rigvir, it is also used in the treatment of advanced melanoma, and exerts its antitumor activity by augmenting immune responses and directly mediating cell death.
In phase I and II clinical trials, the intratumoral administration of talimogene laherparepvec twice a week to patients with various solid tumors was well tolerated. On March 19th, 2013, Amgen announced encouraging results of a Phase III clinical trial in melanoma patients. Significant difference was observed in the durable response rate between the talimogene laherparepvec and the control arm.
Virotherapy was also used for pancreatic cancer. ONXY-015 (dl1520) represents the first replication-competent oncolytic adenovirus that was used in clinical trials for that purpose, which has been engineered to lack expression of the E1B 55 kDa protein (needed to block apoptosis in infected cells). Other adenoviruses lacking the E1B 19 kDa protein were also candidates for pancreatic cancer therapy.
Current and future challenges
Oncolytic virotherapy is not yet a mature field, and incidents were noted where people died or became really ill due to this type of treatment. To make this therapy safe and successful, production rates of viral particles in the infected cancer cells must outstrip the growth rate of the uninfected cancer cells.
There are many benefits to oncolytic virotherapy if researchers can overcome certain drawbacks. The selective nature of virotherapy ensures that healthy tissue is minimally affected, and significant active research is currently being done to improve the accessibility, efficacy and overall safety oncolytic virotherapy.
- Forbes NE, Krishnan R, Diallo JS. Pharmacological modulation of anti-tumor immunity induced by oncolytic viruses. In: Fournier P, Schirrmacher V, editors. Harnessing Oncolytic Virus-mediated Antitumor Immunity. Frontiers Media SA, 2015; pp. 89-100.