Modern Science And New Era Of Oncolytic Viral Therapy

The modern era of oncolytic virotherapy, in which the genetic material of the viruses is modified so as to enhance their anti-tumor specificity, began with a 1991 publication in which a modified herpes simplex virus (HSV) with attenu­ated neurovirulence was shown to be active in a Murine glioblastoma model. Since that first application of virus engineering to an onco­lytic HSV, the pace of clinical activities has been Renovated and has gained a lot of attention, with a lot of clinical trials. 

Evidence for the efficacy of single-agent oncolytic virotherapy is limited, as only very few early phase clinical trials have been conducted. The potential efficiency is, however, supported by several positive reports. In one trial, talimogene laherparepvec, a modified onco­lytic herpes simplex virus was administered by direct intratumoral injection to patients with metastatic malignant melanoma and led to com­plete regression of injected and even non-injected lesions in 8 of 50 treated patients.

In a second trial, an oncolytic vaccinia virus, JX594, which was similarly manipulated, was administered intratumorally to patients with non-resectable hepatocellular carcinoma. Good responses were detected in three out of ten patients.

Recent clinical data look extremely promising

More recently, the report on a phase 1 trial where an engineered measles virus was used in two patients with resistant multiple myeloma was published. The results were highly promising, as both patients responded, showing reduction of both bone marrow cancer and myeloma protein.

It still remains to be seen if the disease will come back in this patient, but at the time of publication the patient was completely fine.

Over the past decade, several viruses have been translated from the laboratory to the clinic, and several more viruses are likely to be used in clinical trials in the near future. Oncolytic viruses are immensely diverse, spreading through tumors and killing tumor cells by multiple mechanisms and with different rate. Each virus has unique benefits and limitations as an oncolytic agent, which may help to determine how it is used. Because of their large size and ability to trigger an immune response, they are constrained by physical barriers and by each patient’s own immune system. Nonetheless, they can also increase the anti-tumor immunity, serv­ing as a cancer immunotherapy. They might even be combined with drugs, radiation, monoclonal antibodies, small-molecule inhibitors, and/or other oncolytic viruses to generate increased efficacy.

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Overall, the field has developed rather slowly, but recent clinical trial data have been promising, and a first-in-class US approval is expected soon for talimogene laherparepvec, which is being tested in a randomized phase 3 clinical trial that has recently completed accrual. It does look like a single-shot cure for cancer is not a wild phantasy, after all!