Toward a future of overcoming intractable cancer with the power of immunity.
Participant Profile
Maiko Matsushita
Professor, Department of Clinical Physiology and TherapeuticsMaiko Matsushita
Professor, Department of Clinical Physiology and Therapeutics
It is said that one in two people in Japan will develop cancer.
While the number of curable cancers is increasing due to advances in early detection and treatment, there are still patients with intractable cancers that do not respond to existing therapies.
As a physician, I have seen a number of patients whose condition initially improved after undergoing aggressive treatment with side effects, only to have their cancer ultimately recur.
This experience has motivated me to work on new therapies to combat intractable cancers.
At the Department of Clinical Physiology and Therapeutics, we are shedding new light on the potential of immunity and conducting research to develop drugs and therapies effective against even intractable cancers.
The immune system in our bodies is a profound world where many elements interact intricately.
It not only responds to pathogens like viruses but also eliminates cancer cells that arise in our bodies little by little every day.
However, cancer cells also have the ability to counter the immune system and proliferate, which is why treatments to overcome this are necessary.
(As of April 2024)
Targeting and attacking cancer stem cells, the "queen bees" of cancer.TCR-T cell therapy is an evolved form of "living drug."
In recent years, various drugs have been developed for cancer, and survival rates are improving. However, there are still cases of recurrence after treatment. To overcome such intractable cancers, we are conducting research using two main approaches.
First, we have been working on the development of a new immunotherapy that targets "cancer stem cells," which are the cause of cancer recurrence. As a result of our work so far, we have discovered multiple antigens that serve as markers for immune cells to recognize these "cancer stem cells."
If we compare a patient's cancer to a beehive, the "cancer stem cells" are like the queen bee. In other words, they have self-renewal capabilities and continuously produce cancer cells, which are like the worker bees. In fact, while cancer cells other than these "cancer stem cells" are eliminated by conventional anticancer drugs, the "cancer stem cells" themselves are resistant to these drugs for various reasons. They survive after treatment and produce more worker bee-like cancer cells, becoming the root cause of cancer recurrence and metastasis. Therefore, we focused on a certain molecule that is specifically expressed in "cancer stem cells." Furthermore, we have succeeded in creating T cells (TCR-T cells) outside the body through genetic modification that can attack cells highly expressing this molecule.
Ultimately, we aim to develop a therapy where T cells isolated from a patient's blood undergo similar genetic manipulation to enhance their aggressiveness against cancer stem cells, and are then returned to the patient's body. Other cell-based medicines using living cells, such as chimeric antigen receptor (CAR)-T therapy, are also well-known. These are called "living drugs" and have recently been attracting significant attention.
Developing treatments that utilize the "dying message" markers left by cancer cells after drug administration.
The second approach is a therapy that utilizes immunogenic cell death (ICD). When anticancer drugs are used, cancer cells are killed. However, depending on the drug used, cancer cells may express markers that are recognized by immune cells during the dying process, which can enhance the immune response against the cancer. We are focusing on this phenomenon of ICD and are searching for drugs that are likely to induce it.
The human body is naturally equipped with many immune cells that attack cancer cells. For example, cells called dendritic cells take in cancer cells and send signals to lymphocytes, causing the lymphocytes to change and attack the cancer cells. Cancer cells evade this mechanism to survive and multiply, but by using drugs that facilitate ICD, it is possible to more strongly activate lymphocytes and improve the precision of their attack on cancer cells.
It has not yet been fully elucidated what kinds of drugs are likely to induce ICD. We have previously reported that some existing anticancer drugs induce ICD in a type of blood cancer called multiple myeloma. Currently, we are screening for other drugs with similar effects. We have already received naturally derived compounds—that is, compounds synthesized from natural sources such as plants—from laboratories both inside and outside the university specializing in organic synthesis, and have identified promising drug candidates.
Ultimately, we aim for research that can return its benefits to patients.To that end, we collaborate with medical institutions, including the Keio University School of Medicine.
The research in our department is basic research conducted in the laboratory using drugs and cells, but we ultimately aim for results that can be applied to patient treatment. We aim for both translational research, which applies basic research to clinical practice, and reverse translational research, which seeks to solve problems occurring in clinical settings through basic research. What is essential for both is collaboration with the medical field. This is made possible in particular by the unique environment of Keio University, a comprehensive university with three medical-related faculties.
International exchange is an excellent opportunity to broaden your horizons.
During your student life, I hope you will take an interest in various things and expand your horizons as much as possible. In that sense, international exchange is one effective way to do so.
During a summer break in my university years, I participated in a one-month hospital practicum at a university in Chicago, USA. There, I frequently visited patients' rooms with a medical team that included a clinical pharmacist, a role rarely seen in Japan at the time. I witnessed firsthand how pharmacists were trusted by physicians and, based on that trust, provided appropriate advice on drug therapy. This experience became the source of my desire to contribute to the training of pharmacists who can be a cornerstone of treatment.
The Keio University Faculty of Pharmacy has several international exchange programs, including student exchanges. Even if you don't go abroad, you can interact with pharmacy students from the United States and Thailand, as we host exchange students from overseas at the Shiba-Kyoritsu Campus. The Keio University Faculty of Pharmacy offers opportunities to broaden your horizons and encounter new worlds.