Photo: Rakuten Founder and CEO Hiroshi "Mickey" Mikitani and Dr. Hisataka Kobayashi, senior investigator at the National Institutes of Health

Hiroshi “Mickey” Mikitani in conversation with Dr. Hisataka Kobayashi, the National Institutes of Health (NIH) senior investigator who developed a revolutionary new cancer treatment called near-infrared photoimmunotherapy. Mickey introduces Dr. Kobayashi and their conversation here.


Mr. Mikitani, what prompted you to get involved in supporting cancer research?

MIKITANI: Four years ago, my father was diagnosed with pancreatic cancer, which is apparently the most difficult kind of cancer to treat. I traveled around the world looking for the most advanced treatment methods to cure my father’s sickness. I read all sorts of papers and met with famous doctors doing research in universities across the globe – Harvard, Stanford, The University of Paris – looking at every option available that could help my father.

I heard of Dr. Kobayashi through one of Rakuten Ichiba’s merchants, Tetsuya Shinbo, an architect running a popular waffle store who came from Kobe, just like me. He told me that he had a relative who was developing a new kind of cancer treatment, and that’s how I met Dr. Kobayashi.

Dr. Kobayashi, after graduating from the Kyoto Graduate School of Medicine and practicing radiology for almost 10 years, you made a rare career move in becoming a researcher.

KOBAYASHI: As a doctor working with cancer, I felt like I was reaching the limit of what I could do with traditional cancer treatments like surgery, radiation therapy and chemotherapy, so I decided to try my hand at fundamental research. Twenty years of research at the NIH eventually led me to a completely new kind of cancer treatment called near-infrared photoimmunotherapy, which singles out and targets only cancerous cells.

The technology has been licensed to Aspyrian Therapeutics, Inc., in which Mr. Mikitani has invested, and it is now conducting clinical trials with the purpose of bringing the treatment to market.

"As a doctor working with cancer, I felt like I was reaching the limit of what I could do with traditional cancer treatments like surgery, radiation therapy and chemotherapy," explained Dr. Hisataka Kobayashi, senior investigator at the National Institutes of Health, of his decision to start researching new treatments.

“As a doctor working with cancer, I felt like I was reaching the limit of what I could do with traditional cancer treatments like surgery, radiation therapy and chemotherapy,” explained Dr. Hisataka Kobayashi, senior investigator at the National Institutes of Health, of his decision to start researching new treatments.

Mr. Mikitani, what prompted you to invest in Aspyrian?

MIKITANI: As soon as Dr. Kobayashi explained to me the basics of near-infrared photoimmunotherapy, I had the same kind of realization as when I started Rakuten Ichiba: “This could work.” I just knew it was the kind of revolutionary treatment worth betting on. It was too late to treat my father, who passed away in 2013, but I believed that if this therapy could make it out of the research phase and onto the market, I could not only “avenge” my father, but also help save cancer sufferers around the world.

When Dr. Kobayashi told me about how he was struggling to raise funds to conduct the trials necessary to bring the treatment to market, I decided to give my financial support.

Dr. Kobayashi, what were your initial impressions of Mr. Mikitani?

KOBAYASHI: When I first met Mr. Mikitani, it was remarkable how much he knew about what was going on in the cancer research world. He was astonishingly quick to understand my explanations of treatment methods that even experts have trouble with, and I was amazed at his understanding of the subject for someone who wasn’t even a researcher or a doctor.

Normally when I explain my work to other professionals, they tell me “there’s no way that treatment would work,” or that “successful experiments don’t mean success in the real world.” I get a lot of negative opinions about such new methods, but Mr. Mikitani had no such preconceptions, and was enthusiastic about it from the beginning.

That happened to be around the time when we were struggling to raise funds for clinical trials at the NIH, and we were having difficulty moving preparations forward. I was so happy to hear that we had Mr. Mikitani’s financial support.

What exactly is cancer?

KOBAYASHI: Cancer is essentially a lump that develops inside your body. A normal human body has an immune system, which protects the body when it finds anything abnormal by sending immune cells to fight it. With most cancers, this approach works fine.

Occasionally, however, the cancerous cells have a kind of backup in the form of “regulatory T cells,” which put the brakes on your immune system. These cells prevent the immune cells that patrol your body from seeing these foreign cancer cells. Your immune system therefore doesn’t work on the cancer, allowing it to become a tumor and spread, making curing it extremely difficult.

Common cancer treatments such as radiotherapy and chemotherapy do work in attacking cancerous cells, but at the same time they also cause serious damage to regular cells. This is why cancer treatment takes such a toll on patients’ health. I have spent my last 30 years as a researcher searching for a method that only targets cancerous cells without damaging healthy ones.

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“As soon as Dr. Kobayashi explained to me the basics of near-infrared photoimmunotherapy, I had the same kind of realization as when I started Rakuten Ichiba: ‘This could work,'” said Rakuten Founder and CEO Hiroshi “Mickey” Mikitani.

How does “near-infrared photoimmunotherapy” target only cancerous cells?

KOBAYASHI: There are two methods. The first method attacks the cancerous cells directly.

In this method, a special antibody, which only binds itself to the protrusions found on cancerous cells, is chemically joined to a photosensitizer called “IR700” and injected into the bloodstream. The antibody then traverses the body together with the IR700, finding and “docking” on to cancerous cells.

By locating the docked cells and shining near-infrared light on them, the IR700 undergoes a chemical reaction which pierces the cell membrane, allowing water through the perforation and causing the cancerous cell to expand and rupture in a matter of seconds, effectively eliminating it.

Are there any side effects, like those presented by chemotherapy or radiotherapy?

KOBAYASHI: Practically none. Near-infrared light is what you use in your TV remote control – it is harmless to humans. Only a small amount of the IR700 antibody conjugate is used, and even if they dock themselves on to healthy cells, no damage is done if we don’t shine near-infrared light on them.

In April 2015, the treatment was approved for clinical studies by the U.S. Food & Drug Administration (FDA), and human trials (phase 2) will soon be over.

MIKITANI: The results so far have been astounding. Seven patients suffering from inoperable recurrent head and neck cancer participated in the trial, and the cancerous tissue was necrotized in all seven cases, without even relapsing in four cases.

The success rate for existing medicinal treatments is only around 7% to 12%. Even the immunotherapy drug “Opdivo,” which has been getting a lot of attention lately, is only around 23%. The near-infrared photoimmunotherapy success rate of around 80% is just astonishing.

Is “near-infrared photoimmunotherapy” only able to treat head and neck cancer?

KOBAYASHI: We can expect a similar effect on other types of cancer as well, but since the antigens produced by the targeted cancerous cells are different depending on the type of cancer and the person, we will need to use some new types of antibodies in order to make the treatment work for all types of cancer. If that happens, I believe we will be able to treat around 80% of cancers, including esophageal, bladder, colon, liver, pancreatic and kidney cancer.

What is the other method for eliminating only cancerous cells?

KOBAYASHI: This method destroys the regulatory T cells that keep the cancer hidden from the body’s immune system.

We combine “IR700” with an antibody that bonds with regulatory T cells. By shining near-infrared light on the bonded antibodies once they are inside the tumor, the regulatory T cells hiding the cancer are destroyed, leaving the cancer completely exposed to the body’s own immune system. The patient’s immune system is then able to attack and kill the cancerous cells. With this method, it’s possible to treat more cancer with less antibodies.

What role will Rakuten play in this revolutionary cancer treatment?

MIKITANI: I am taking an active role in Aspyrian’s management, and I frequently visit their San Diego headquarters. In my management role there I am working to making near-infrared photoimmunotherapy publicly available, and I think Rakuten will be able to provide support in bringing the treatment to market.

KOBAYASHI: Without Mr. Mikitani’s support, we probably wouldn’t have been able to move forward with trialing near-infrared photoimmunotherapy. Partnering with Rakuten on the business side will also be extremely important.