On August 24th, a reporter was informed from Prof. Guangmei Yan research group at Zhongshan University that this group of researchers identified and gained oncolytic virus M1 synergist with accurate treatment of biomarkers. They found that a kind of small molecule compounds of targeting ERAD pathway can significantly enhance the anti-tumor activity of oncolytic virus M1 by 3,600 times. The finding was published in the International Journal of Science Translational Medicine on 24th.

Oncolytic virus M1 was found on mosquitoes in Hainan Island of China. Over the years, Guangmei Yan team carried out many studies on the selective infection and various cancer cells killing ability of M1 virus. In 2014, researchers revealed that the anti-tumor mechanism of M1 virus was to identify zinc-finger antiviral protein (ZAP) which was widely lost in cancer cells, and then leads to cell apoptosis caused by endoplasmic reticulum stress. Scientists had shown that the M1 virus was effective to many cancer cells, including liver cancer, colorectal cancer, bladder cancer and melanoma. However, it was still facing the challenge for being used in clinical practice of that tumor had different sensibilities on different organs and to various drugs.

Guangmei Yan told the reporter that in the recently published paper, it showed that a small molecule compound can help M1 virus overcome the heterogeneity of tumor and obtain stronger effect. After screening hundreds of clinical anti-tumor small molecule chemical drugs, the researchers found a class of small molecule compounds targeting ERAD pathway which can significantly enhance the anti-tumor activity of M1 virus up to 3600 times, called “Strong Oncolytic Virus Synergist”. This effect was validated in both the in situ liver cancer model of mice and in vitro cultured tissue of surgical specimen derived from clinical tumor.

Meanwhile, whether this synergist is suitable for combining with oncolytic virus M1 to apply on patients can be predicted by a VCP protein of ERAD pathway. “The high expression of VCP protein in tumor tissue from surgical resection of patients, suggest that the patient is suitable for the oncolytic virus M1 and ERAD inhibitor combination treatment, while low expression of VCP suggest that the patient is not suitable.” Guangmei Yan said, “ERAD inhibitor achieved ‘precisely synergize’.”

In addition, the team confirmed the safety of M1 virus and ERAD inhibitors on non-human primate cynomolgus monkeys. They also found that M1 virus induced tumor cells to release cell toxicity factor, along with SMCs, killing the tumor cells that had not yet been infected with the M1 virus to achieve “tumor killing”. The results were published on Proceedings of the National Academy of Sciences on June 27, 2017.

These results suggest that this therapy has great potential for the treatment of liver cancer which has high morbidity, high mortality and lack of effective drugs in our country. It brings new hope for refractory liver cancer and expected to apply for clinical trial approval next year.

Known more about oncolytic virus, see oncolytic virus therapy development.