Akimasa Seno, Ph.D., President, The Laboratory of Natural Food and Medicine (LANFAM), Co., Ltd.
“Better future for cancer patients”
Cancer is one of the largest problems in this world. Millions of people are suffering from it, but there
is no fundamental treatment. The problem might be based on current cancer researches. Most casesof them including anti-cancer drug screening are depending on cancer derived cell lines and theircancer gene mutations.
[Hypothesis & Test]
A Japanese cancer researcher artificially induced cancer on rabbits' ears by continuous inflammatory
stimulation around 100 years ago. Cancer stem cells (CSCs) have recently been identified andcurrently considered to evoke cancer and its relapse. CSCs are believed to be resistant to chemo- andradio-therapies. Collectively, we raised a question, “Could chronic inflammatory environments
induce CSCs?”
To evaluate this hypothesis, we used conditioned media derived from cancer cell lines mimicking
chronic environment, because cancer cell lines often secrete inflammatory factors such as growthfactors, cytokines and chemokines. Stem cells were treated with the conditioned media for 4 weeks
to create CSCs without intended introduction of cancer-related gene or mutations. Thus, the createdcancer stem cells (cCSCs) have always been assessed for their characteristics of self-renewal,
pluripotency and tumorigenesis as well as drug resistances. We take these CSCs created by the effectof environmental conditions as the models of naturally developed cancer in vivo.
While different methods are found to establish CSCs, our method has a unique advantage that
normal cells from not only cancer patients but also healthy people could be converted into cancer
stem cells. The resultant cells would maintain the genetic background of any original cells.
[How cCSCs could be used]
Once cCSCs are established, they can be applied for the conventional analyses such as drug screening
and gene comparison. Since the cCSCs keep gene backgrounds of donors, the data could be fed backto them directly. In this context, cCSCs can contribute to establish the strategy for “precisionmedicine” and “personalized medicine”. Even more, when the stem cells are provided from healthypeople, we can convert them into cCSCs, which will be the model of CSCs reflecting the cancer thatthe donor might develop. This means the data might personally help diagnose themselves even inthe future. This is the reason why we propose the development of the predictive treatment of cancer,
to which the cCSCs can contribute.
[Current members and situation of LANFAM]
We are supported by the organizations of small and medium enterprises and the regional innovation.
Our research currently depends on the facilities of Okayama University. LANFAM was establishedwith our personal funds. Our representative director, Yoshio Shimizu, funded the most. He wasimpressed by the idea of cCSCs and aspired to establish a method to predict CSC development. I,Akimasa Seno, work here as a president and performs experiments in the technical advisor’slaboratory. I joined his group with some interests in his cCSCs idea. Since our technical advisor,Professor Masaharu Seno, will retire from Okayama University next year, his laboratory will be closed
and will not be supported by the university. We are looking for a new research place.
[Our scenario of using cCSCs and current collaborators]
We are now just continuing to create cancer stem cells and research on them, focusing on how we
can induce cCSCs. Researchers in Wayne State University in the US already have some interests in
our cCSCs and already started collaborative studies with us. COSMO BIO Co., Ltd. is now planning to
distribute our cCSCs. The cCSCs market is limited to a small number of researchers in the current

stage. Once it has got started to be provided, the importance will be spread to be known much morethan ever before. We believe the market can be expanded to serve all people, not only researchers
but also the others including both patients and healthy people, who are interested in their own CSCs.
We are now looking for collaborators, funds and places to continue our work. Also, we are looking
for stem cell providers, cCSC distributors, and other business partners. We do hope that theaccumulated data with our cCSCs will be used for cancer predictions of all people.
[Q & A]
Q1.
cCSCs keep the original genomic background and there is no gene modification. The question is, “Is
it your original idea?” Or “Is there any people or group in the world who are trying to create thecCSCs?”
A1.
The idea of cCSC is a very unique idea of Prof. Masaharu Seno who is our technical adviser, and noone other than our collaborators is trying to create cCSC yet. Since it takes at least 3 weeks toestablish one cCSC line, we have to take so much care of the cells for successful results. Although thistechnique is not so much difficult, not so many people are able to handle the cells with concentrated
care.
Q2.
I suppose the concept is used to screen drugs or other things. Are you going to take blood and analyze
serum or something? Is that the approach? I think there was a slide showing that you're going toscreen drugs.
A2.
I meant our cCSCs could be applicable for conventional analyses and purposes. Drug screening is oneof them, which we will perform with established cCSCs. If you want to screen drugs with your own
cells, you have to provide us some stem cells and we’ll convert them into cCSCs. The use of bloodother than blood transfusion is currently prohibited in Japan by law.
Q3.
It would be much easier for pharma companies to collaborate with you if you can identify a certain
molecule that makes cCSCs.
A3.
Yes, exactly. We are analyzing that at the same time, and we are now finding some molecules which
can induce cCSCs.
Q4-1.
After the two mentoring sessions, the presentation itself was drastically improved very much. But
still, of course, I must make some comments. I want to ask you to see the real market. Cancer market
is very huge, but the marketing size of your products will probably be 0.1 percent or less than that. I
cannot help asking how many other people or how many industries are involved to this end. Youneed to explain how you can contribute to a pharma in their drug discovery process. You will haveto translate your research result into the proposition with business value. To accomplish thissuccessfully, I think you will also need some partners to have those kinds of discussion many, many,many times, like, tens, or hundreds. All kind of the meetings will be necessary. And at the same time,
I really strongly appreciate if you can propose a specific type of cancer to focus on. Starting analyses
on a specific type of cancer, I think there will be more people who can share more questions on theavailability of cCSCs in the same field. Then, the pharmaceutical company can make some proposal
to them, even for the basic studies at least. At the beginning they are already segregated into thearea of some specific types of cancer. It's up to you to decide which part of the pharmaceuticalcompanies to tie up with. It’ll be really appreciated if you can make a little more effort to decide
where to start.
A4-1.
We are still looking for such a partner who can discuss with those problems. But I know there are somany small cancer markets and most of them are not focusing on cancer stem cells and many
researchers are focusing on cancers developed in specific organs. However, I believe that problems
in cancer treatment wouldn’t be solved if we only continue to focus on cancers separated into theirorgans as most of the cancer scientist have done up to now. I must tell you that cancer could beclassified into 6 types regardless of organ; adenocarcinoma, squamous cell carcinoma, sarcoma,
leukemia and lymphoma including myeloma and glioma. Our cCSCs could be differentiated into every
type of those cells if we use pluripotent stem cells from the beginning. It means there should be nogap among organs. Our final aim is to establish fundamental treatment of all types of cancer, notorgan specific. On the other hand, we can provide organ specific cCSCs also when we use organ
derived stem cells and/or organ specific microenvironment. The demand should be depending on
customers but not on us, suppliers. We will be just ready to follow the customers’ choice.
Q4-2.
No, you must decide it. And of course, you must understand the type of cancer and cancer stem cell
itself is merely a concept. Because cancer stem cell is still controversial, some people will
immediately doubt and not try to use cCSCs even you start to deal with cancer stem cells. Therefore,
you must be careful to choose your words to appeal. I have many things to think about.
A4-2.
Even though there’re a lot of people who do not believe in cancer stem cells, cancer stem cells are
truly existing and it could be a cancer treatment target. I must feel nothing have been done at pharmasides and we have to keep explaining how it is important until the information on the importance ofCSCs is sufficiently shared. Moreover, some companies have successfully been establishing patientderived cancer stem cells regardless with their origins. There will be no doubt on our cCSCs to becommercialized as business if both classified phenotypes and tissue specific phenotypes have been
focused.