Stakeholders Engagement

Dialogues with Stakeholders (2018)

Innovation and Partnerships for Creating Future Shared Value

Due to the mountain of society challenges in the healthcare eld, there is great anticipation for revolutionary innovations. Therefore, we invited Dr. Hisataka Kobayashi, Senior Investigator at the National Cancer Institute (NCI) in the United States, who developed a cancer photoimmunotherapy method that kills cancer cells by irradiation with near-infrared light, to discuss the innovation and the role of Shimadzu technology in treating cancer. The following is from a conversation between Dr. Hisataka Kobayashi and Takashi Marume, General Manager of the Healthcare Business Strategy Unit in Shimadzu's Corporate Strategy Planning Department.

Date May 15, 2018
Location Shimadzu Corporation, Sanjo Works

Marume: Currently we are in the second year of Shimadzu Corporation's 3-year medium-term management plan. Originally, the previous medium-term management plan was based on solving challenges faced by customers, but the current plan is based on solving challenges faced by both customers and society in general.
Based on that focus, the plan specifies four important growth fields. One of those fields is healthcare. Shimadzu intends to create additional value by combining X-ray image processing technology, which is your expertise, with mass spectrometry technology, which is one of the core technologies of Shimadzu, and then use it to offer comprehensive healthcare support for everything from routine health management to nursing care. Shimadzu refers to this field as "advanced healthcare." Therefore, beginning last year, Shimadzu has been busy starting various research, development, service, and new businesses in the advanced healthcare field. Today, we hope to hear various ideas and comments you may have about such applications

1. Photoimmunotherapy for Cancer

Marume: Could you provide a simple explanation of photoimmunotherapy for cancer?

Dr. Kobayashi: Photoimmunotherapy is a technique for reducing the number of cancer cells and actively increasing the body's immunity against cancer. In other words, the basic concept of the treatment is to reduce enemy forces and strengthen friendly forces. Therefore, in order to destroy only cancer cells without damaging normal cells, we devised a technique for attaching chemical substances to antibodies that specifically target cancer cells and then activating the antibodies with light. We also modified the method used to destroy the cancer cells. Using conventional methods of destroying cells with drugs takes time, mummifies the cells, and does not stimulate the immune system. In contrast, if cells are physically destroyed within the body, the cell debris stimulates the immune system. If the debris is something that was not previously recognized in the body, it not only increases the variety of immunity, but also serves as a key to starting new immunity.

Photoimmunotherapy for Cancer
That means that destroying cancer with light provides a method for actually improving immunity by increasing the number of substances recognized by the immune system, even for substances not previously recognizable by the body, and stimulating the immune system.

Mechanism of How Cancer Photoimmunotherapy Works

Mechanism of How  Cancer Photoimmunotherapy Works

2. Background for the Research

Marume: Did that idea occur to you suddenly one day? What was the thinking process that resulted in the concept?

Dr. Kobayashi: I used to be involved in treating cancer patients with radiotherapy and even wrote research papers on radiotherapy. At the time, radiodiagnostics and radiotherapy were performed within the same department and we were trying to find ways to combine them. Later, when I became a researcher, I decided to create a treatment method that only killed cancer cells, to extent possible. That resulted in trying to create a method that did not simply kill cancer cells, but that also created systems within the body that would enable a full recovery. Therefore, I ended up successively trying various combinations in an effort to identify methods that destroyed cancer cells as successfully as possible and destroyed them in a manner different than by conventionally using drugs, so that other systems in the body could also be utilized.

Marume: Once the concept occurred to you, what did you do next to realize the system? Please explain the "how to" portion of that process.

Dr. Kobayashi: I thought of using antibodies that are specifically attracted to cancer cells. I had previously been involved in researching the behavior of antibodies, so I was very familiar with how different sizes of antibodies behaved.

Marume: How much basic research did you do?

Dr. Kobayashi: I became involved in studying antibodies in 1984, when I started taking pathology classes in my fourth year at university. Given the high specificity of antibodies, I wondered how that characteristic could be used to transport something to cancer cells to treat the cancer.
When I returned to Kyoto University for graduate school, my work involved researching methods for killing cancer cells by attaching radioisotopes to antibodies for delivery to the cancer cells. My doctoral dissertation was about how to improve such methods. Next, given that normal cells are irradiated when radiation enters the body, I wrote a thesis about how to generate antibodies as quickly as possible, and more specifically, how to generate radioisotopes as quickly as possible. However, it is difficult to control antibodies before they reach the cancer, because they must flow through the blood.
I continued that research at the NIH (National Institutes of Health), however the conclusion eventually reached from the research at NIH and other joint research was that injections of a toxic substance will always affect normal organs. Therefore, I realized the injected substance needs to be non-toxic, but controlled so that it becomes toxic, so now I am researching methods for switching the toxicity ON/OFF

Marume: So it wasn't a sudden realization, but rather a logical accumulation of many elements.

Dr. Kobayashi: Consequently, it has continued for 34 year.Initially, I focused on how the chemical substances interacted, but eventually aborted that approach because it meant both the first and second agents are chemical substances and so the treatment would require obtaining approval for two drugs, which would be a major undertaking, and because of the presumed quantitative limits on how much of a foreign substance could be introduced in the body.
In that case, I thought, if the first agent is a drug, then the second agent should be some sort of physical energy, so I started searching for a suitable physical energy. That resulted in concluding that near-infrared light offered the most potential.
The next step involved searching for a chemical substance that could be switched ON/OFF with light energy from the absorption of near-infrared light. That process led us to the drug we are currently using, which enabled the system for delivering the drug by antibodies.

Marume: I see. So, the purpose for the drug was determined first and then you searched for the drug to fit that purpose? It must have taken a long time to search through all the possible combinations and drugs before reaching a successful solution. What was it that kept your motivation level up through that process?

Dr. Kobayashi: The biggest factor was that I love research. I was also motivated by a strong desire to help cure patients. In other words, I think my desire to leave something from my medical research that would help patients, even a little, was a significant motivation.

Marume: Given that Shimadzu Corporation also has specified a management principle of "Realizing Our Wishes for the Well-being of both Mankind and the Earth," we share a similar motivation to help save patients through healthcare and medical technology.
Next, could you summarize some of the ways Shimadzu has been involved during that process of developing your photoimmunotherapy method?

Dr. Kobayashi: It began when Mr. Hattori was President. When I talked about how the use of light potentially could be expanded into medical treatment applications, not just imaging, President Hattori showed strong interest.
Since then, I have obtained help from Shimadzu in various situations that required the help of professionals, such as to analyze polymers.

3. Latest Update and Future Outlook for the Research

Marume: What is the current status and future plans for the research? I understand the method is currently in clinical trials, but how much longer will those trials take to complete?

Dr. Kobayashi: In the United States, we finished phase 2 and are currently in phase 3, so it won't take that much longer. In Japan as well, trials have started at the National Cancer Center Hospital East, which should be completed quickly, provided the first trial is successful.

Marume: Does that mean that, if all goes well, it might be released soon? Will you expand its scope to include other types of cancer, for example?

Dr. Kobayashi: In terms of expanding the scope using the same type of antibody, yes, of course we are planning to expand the scope. Severe breast cancers and other conditions that are currently not adequately treated using anticancer agents should also provide good targets.

Marume: It seems the method offers only benefits for the patient, such as no pain, no adverse effects, quick efficacy, and improved immunity.

4. Shimadzu Corporation

Marume: How can Shimadzu help with your research in the future? What are your expectations?

Dr. Kobayashi: We would appreciate help with clinical trials, of course. For example, I would be especially grateful for help with using a LIGHTVISION imaging system (see note) to image the high specificity of antibodies targeting cancer cells. Furthermore, the LIGHTVISION system also shows the attenuation and disappearance of fluorescent light, which can be used as evidence that chemical reactions occurred. I think that objective understanding would help ensure the likelihood of success, for both the patient and physician. It would also be extremely helpful to have an opportunity to make a commitment at the clinical imaging stage, such as by using a mass spectrometer to measure substances in the urine or check for biomarkers, for example, after treatment.

Marume: Do you have any opinions or advice regarding Shimadzu's measures to integrate analytical and medical technologies, as I mentioned earlier regarding the advanced healthcare field, to develop and release technologies for not only medical applications, but also for health management?

Dr. Kobayashi: I think integrating such technologies will generate new information not previously available. If physicians need to treat a patient, they will appreciate having more information. For example, it would be great if there was a system that could tell the physician which antibiotics will be most effective for each patient, based on checking for biomarkers before starting a treatment.

Marume: Do you mean individualized medicine or patient-customized treatment?

Dr. Kobayashi: Yes, exactly. Patients would be much easier to treat if we could determine their immune system status in advance. In other words, if biomarkers could be used to perform a diagnosis before surgery, based on both immunological and tumor data, physicians could provide better treatments.
To avoid overwhelming physicians with information, it would be even better if only selected data was provided immediately to physicians when they are treating patients. The biggest problem is that the amount of available data has been increasing so much that it is difficult to determine which information is useful.

Marume: Do you mean an AI-based system that can select important data from large amounts of collected data and interpret the data?

Dr. Kobayashi: It would be great to have a system that could extract from large amounts of data just the information of interest to the physician and then quickly deliver it to the location where the physician is providing treatment.

Marume: Is delivering it quickly to the treatment location the key point?

Dr. Kobayashi: I think the fact that I spent a lot of time on-site where patients are being treated was probably a major factor that resulted in developing my treatment method. There are many things that can only be learned from being on-site, such as identifying the true problems and what things are necessary in reality. I recommend gathering lots of feedback and opinions from those actually using the products.

Marume: That applies to all of Shimadzu's measures, not just advanced healthcare, doesn't it?

Dr. Kobayashi: Healthcare is a very big field, so if you can successfully identify things that are truly necessary, I think people working in healthcare will be extremely grateful.

Marume: After all, working with a wide variety of people to solve their problems and being useful to society and individuals is what Shimadzu's corporate philosophy is all about, so we look forward to spending time on-site where Shimadzu products are used.

Voice of a Stakeholders (2016)

With the Paris Agreement concluded at the 21st meeting of the Conference of the Parties of the United Nations Framework Convention on Climate Change (COP21), it can be said that the world has started shifting from a low-carbon society to a "carbon-free society."
Now, the method of backcasting, which is to depict a vision (ideal future image) and set mid- and short-term goals based on that vision, is being required more than ever, and I will pay close attention to Shimadzu's efforts in the future, especially what goals are set and how activities are conducted. I believe that measures from the point of view of the value chain, including customers and suppliers, as well as business continuity planning (BCP) responding to the risk to energy supply, will also contribute to the reduction in CO2 emissions.
I really hope that the spirit of Shimadzu, which has made a significant contribution to local communities for a long time, will continue to remain as it is for future generations.

Shizue Hattori
Professor of the Department of General Humanities,
Faculty of Humanities Kyoto Seika University

 

Shizue Hattori Professor of the Department of General Humanities

For the first time since the last visits in the autumn of 2011 and spring of 2012, I came to the "Shimadzu Corporation Forest" in Nantan City, Kyoto, and was greatly impressed with its transformation and beauty. Thanks to tree thinning, the artificial forest of Japanese cypresses has improved, with better space for airflow, bringing in sufficient sunlight. What concerned me slightly, though, were the natural forests such as Prunus grayana, which are distributed over the lower stretches of the water catchment area.
This was because, in contrast to the upper-layer trees covering the top, there were no lower-layer trees, which there should have been in the middle or lower layer of the forest.
Having said that, seeing youngsters practicing a rugby club in SHIMADZU drill so vigorously that their voices sounded as if trees were falling, I had a feeling that I can rely on future generations to take care of the forest.
The best part of this forest is that you can spend an enjoyable time there with your family.

Shigeru Matsutani
Honorary Curator of the Kyoto Prefectural Botanical Garden
Guest Professor at Kyoto Prefectural University

 

Shigeru Matsutani Honorary Curator of the Kyoto Prefectural Botanical Garden

Dialogs with Stakeholders (2015)

We invited some influential individuals to have a dialog about Shimadzu's Environmental and Social Report and Shimadzu's activities in general. The following is a selection from the valuable views expressed during that dialog.

Date April 24, 2015
Location Shimadzu Corporation, Sanjo Works
Overview After touring the production plant facility, the product showroom, and so on, they exchanged views with
Deputy Dean, Professor,Faculty of Safety Science,Kazuhiko Takano

Comments from an Outside Expert (1)

Kazuhiko Takano
Deputy Dean, Professor,
Faculty of Safety Science,
Kansai University

I was impressed with Shimadzu's stance on creating products with high added value while striving to satisfy the needs of customers. The report conveys the sincerity and earnestness of Shimadzu. I think the report is wonderful just as it is, but I think corporate value could be further improved by giving more detailed information about company activities to give a better impression, such as regarding corporate social responsibility. That would simultaneously help increase employee motivation and also be important in terms of compliance.
For example, Shimadzu pioneered using control self-assessment practices for risk management. You were also a leader in adopting business continuity planning, corporate governance, and information security practices. I think information about such measures should be included as well. Lately, such information is also important to investors, so I hope the report will indicate that such measures are escalated each year as improvements are made going through PDCA cycles.

Associate Professor,Emi Sugawara

Comments from an Outside Expert (2)

Emi Sugawara
Associate Professor,
Faculty of Law,
Osaka University of Economics and Law

I think the report put more focus on social aspects than the one in 2012 when I participated in your stakeholder dialogue. However, diversified stakeholders have been engaging in evaluation of business activities lately, so it is ever more important for business to provide transparency. In order not to lead to misunderstanding among stakeholders that a lack of information means a lack of activity, information of activities should be proactively disclosed.
Apparently, Shimadzu has developed internal systems such as work-life balance programs and diverse employment for foreigners, so one of pillars for the next report should be "diversity in the workplace", which would shows Shimadzu's policy to be a better place to work for a wider variety of people. I believe that it send a strong message to those interested in working at Shimadzu and also to your current employees.
As the next step, I hope that Shimadzu will establish and implement "social" management systems in addition to environmental ones (EMS), and that you will describe how Shimadzu activities and products are involved in helping people around the world achieve their environmental and health rights.

Response to Views from Outside Shimadzu

We want to sincerely thank Professor Takano and Associate Professor Sugawara for generously taking time from their busy schedules to come to Shimadzu and offer their valuable insights.The information they provided about current topics and world trends in their respective elds of expertise was extremely stimulating to relevant personnel at Shimadzu. It has provided an invaluable opportunity to renew our awareness of certain issues, such as issues that we need to buckle down and improve further in the future and the importance of including information that would be effective in increasing Shimadzu's corporate value.
Shimadzu remains committed to merging scientic technologies available to Shimadzu with environmental and social measures to contribute to society through our business activities.

Ichiro Kowak
Senior Corporate Executive Of cer and Director of Shimadzu Corporation

  • * Director and Senior Corporate Executive Officer at the time the meeting was held in April 2015