Professor Tasuku Honjo of Kyoto University said he was expecting a good outcome out of more than 1,000 clinical trials on combination therapies to improve the effectiveness of immunotherapies. He won the 2018 Nobel Prize in Physiology or Medicine for his identification of programmed cell death protein 1 (PD-1).

“Soon, cancer will be regarded as a chronic disease,” he said.

Professor Honjo was one of the speakers at 2019 Seoul Bioeconomy Forum held on Thursday, organized by the Ministry of Health and Welfare and the Ministry of Science and ICT.

Professor Tasuku Honjo of Kyoto University speaks at 2019 Seoul Bioeconomy Forum in Seoul, on Thursday.

He had a plenary lecture on “Discovery and Impact of Cancer Immunotherapy by PD-1 Blockade.”

Based on his research, drugmakers BMS and Ono Pharmaceutical were able to embark on developing anti-PD-1 immunotherapy Opdivo (nivolumab).

In early clinical trials, he said, it was not easy to recruit patients due to the distrust of immunotherapy. He started the tests in 2006, but the paper was out in 2012. The time was delayed, but he had surprising results. Patients with solid cancers such as non-small cell carcinoma and melanoma showed high response rates and the drug in those who responded remained effective even years after the discontinuation of the treatment. In particular, the more mutations cancer had, the better the treatment worked.

“Theoretically, immunotherapies only stimulate the immune system and thus not harm normal cells. Once they work, their effects last for a long time, and some can hope for a complete cure,” Honjo said. “If a certain type of cancer has many mutations, immunotherapy can treat it. Immunotherapies changed the paradigm of anticancer treatment.”

Opdivo is used in various cancers, including melanoma, lung cancer, kidney cancer, and bladder cancer. In recognition of this achievement, Honjo became the Nobel laureate in Physiology or Medicine last year, along with Professor James Allison of the University of Texas.

Honjo said the research on immunotherapies has just begun. More research is needed to increase the effectiveness of immunotherapies, he said.

The limitation of immunotherapies is that only 20 to 30 percent of patients respond to the treatment. It is not known precisely in which patients immunotherapies show strong potency. Researchers are studying to reveal this around the world.

The Japanese expert emphasized that researchers need to find a biomarker that responds to immunotherapies. "The current PD-L1 expression rate has too many exceptions that it's hard to see it as a powerful biomarker. We have to secure a biomarker related to a personal immune system,” he said.

It remains a challenge to identify the right partner drug that will create synergy with immunotherapy.

“Many researchers are combining immunotherapy with chemotherapy or radiation to raise the therapeutic effectiveness. I expect that achievement will come out of about 1,000 clinical trials,” he added.

Recently, he is working on a combo of Opdivo with hyperlipidemia treatment bezafibrate. In finding a way to activate mitochondria that stimulates T cell proliferation, Honzo came up with an idea of using bezafibrate with Opdivo to increase mitochondria by increasing the expression level of PGC-1α.

He confirmed a possibility that the combo of bezafibrate and Opdivo could increase the cancer-fighting effect. A clinical trial is underway in Japan to prove this.

A recent study showed that PD-1 also affects the intestinal microbial environment and neurotransmitter secretion. However, which mechanism is expressed in the veil is still unknown. Thus, it is necessary to study the side effects of immunotherapies in the future, he said.

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