By Deena Beasley

(Reuters) - In a phase II trial in patients with advanced hepatocellular carcinoma, high doses of a genetically engineered smallpox vaccine led to significantly longer survival compared to lower doses.

Dr. Tony Reid of Moores UCSD Cancer Center at the University of California, San Diego reported the results in San Francisco on Saturday at a meeting of the American Association for the Study of Liver Diseases.

Patients given high doses of the altered vaccine, being developed by privately held biotech company Jennerex Inc and known as JX-594, lived for a median of 13.8 months compared with 6.7 months for patients treated with one-tenth of that dose.

The small 30-patient study found that 66% of the high-dose patients were alive after one year, compared with 23% of the low-dose group.

Temporary flu-like symptoms were the main side effect seen in the trial.

Scientists have been intrigued for decades with the idea of using viruses to alert the immune system to seek and destroy cancerous cells. That interest has taken off in recent years as advances in genetic engineering allow them to customize viruses that target tumors.

JX-594 is derived from a strain of the vaccinia poxvirus, once commonly used to vaccinate children against smallpox.

"Viruses are inherently cancer selective and tumor cells are inherently susceptible to viral attack," said Dr. David Kirn, chief medical officer at Jennerex. "We enhance selectivity by further attenuating and weakening the virus in normal tissue."

In material released to the public, the company says it deleted the thymidine kinase (TK) gene from the virus to enhance its cancer cell selectivity, "making it dependent on the cellular TK expressed at persistently high levels in cancer cells." And to make it more efficient, "JX-594 is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to...tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack."

Dr. Kirn said the first patient has been enrolled in a Phase 2b study comparing JX-594 with standard care in 120 liver cancer patients who have stopped responding to sorafenib (Nexavar, Onyx Pharmaceuticals).

Patients in the trial will first be given an intravenous infusion of JX-594, followed by direct injections into the tumor. Dr. Kirn said the trial will also allow for more continuous dosing than in earlier studies.

Jennerex plans to launch next year a phase III trial comparing JX-594 with Nexavar and is conducting earlier-stage trials in other types of cancer.


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