Harnessing the Immune System to Cure Cancer

2026/05/28

What if you could cure cancer using the body's own immune system? CAR-T cell therapy, a form of immune cell therapy that uses living immune cells, has proven highly effective against blood cancers such as lymphoma and leukemia. Yet current immune cell therapy cannot treat all types of cancer. Professor Yuki Kagoya of the Division of Tumor Immunology at the Institute for Advanced Medical Research is working to bridge the gap between basic research and clinical application, with the goal of making immune cell therapy accessible to more patients—and ultimately conquering cancer.

Cancer immunotherapy, which uses the immune system to treat cancer, is gaining recognition as the “fourth cancer treatment modality,” alongside surgery, chemotherapy, and radiation therapy. A prime example is immune checkpoint inhibitors, drugs that release the brakes, such as PD-1/PD-L1, that cancer cells place on immune cells, unleashing their ability to attack.

Prof. Kagoya’s research focuses on immune cell therapy, which involves genetically modifying immune cells to boost their attacking power and directly target cancer cells. In CAR-T cell therapy, T cells are extracted from the patient and equipped with CARs (chimeric antigen receptors) that recognize markers on the surface of cancer cells. The modified cells are then cultured and expanded in the lab before being infused back into the patient to attack the cancer directly. This approach has shown remarkable efficacy against blood cancers, including lymphoblastic leukemia and malignant lymphoma, and has been covered by national health insurance since 2019.

"The results in blood cancers have been remarkable. Some blood cancers that were previously untreatable can now be driven into long-term remission, and in some cases may even be cured. But challenges remain: the cost is extremely high, side effects can be severe, and relapse after remission is a real concern. The biggest problem, however, is that it is ineffective against most solid tumor cancers. We’re working to improve the effectiveness of immune cell therapies, including CAR-T, with the ultimate goal of developing treatments that can completely cure any type of cancer."

"Immune cell therapy uses living cells, which is why it’s called a ‘living drug.’ Conventional drugs lose their effect once they are broken down in the body, and it is often unclear whether they have actually reached the affected site. There is also the issue of drug resistance, in which medications eventually stop working.

Living cells, by contrast, can multiply where they're needed and adapt to their environment. What's more, even after the cancer cells have been destroyed, these immune cells survive and continue to stand guard. When you think about it that way, I believe cell-based therapies like immune cell therapy are what it will take to completely cure the difficult cancers we can’t treat today."

Prof. Kagoya has high hopes for the development of immune cell-based therapies and drugs. With the ultimate goal of conquering cancer, he pursues his research on immune cell therapy through two main approaches.

The first is understanding T cell properties at the genetic level to find better ways to modify them. Cell properties are determined by roughly 20,000 genes and can shift dramatically depending on molecular interactions. Using gene editing technologies like CRISPR/Cas9, the team is working to enhance T cell "quality" by manipulating target genes.

The other is the development of artificial genes. It is now possible to design and build genes artificially from scratch using DNA, cells, and other biological components as building blocks, a rapidly advancing field known as synthetic biology.

“Just because it is immune cell therapy does not mean we need to rely solely on natural immune cells. CARs themselves are artificial genes, designed and built to recognize specific cancer cell markers. We design genes ourselves with specific goals in mind—acquiring targeted functions, overcoming resistance, and more."

For genetically modified T cells returned to the patient’s body, persistence, defined as the ability to keep working as long as possible, is critical. This sustained activity helps maintain therapeutic efficacy and prevent recurrence and metastasis. However, research has shown that T cells become exhausted over the course of prolonged treatment.

“This phenomenon was originally discovered by researchers studying viral infections. In prolonged infections such as HIV and hepatitis, T cells that continuously exert immune functions gradually lose their effectiveness. This phenomenon is referred to as exhaustion. The same kind of exhaustion has been observed in T cells fighting cancer, so we’re also working on ways to prevent it."

T cell exhaustion involves molecules like PD-1 that put the brakes on immune cells. But targeting PD-1 alone doesn’t fundamentally prevent exhaustion or restore T cell function. Prof. Kagoya and his team turned to the epigenome—a system that alters gene expression through chemical modifications to DNA and histones without changing the genetic code itself. They are now working on regulating epigenomic factors linked to exhaustion and reprogramming exhausted T cells to restore their function.

Another important research theme is the treatment of solid tumors. CAR-T cell therapy has proven highly effective against blood cancers. But it has yet to show results against solid tumors, such as stomach, lung, and colorectal cancers, which make up the vast majority of cancer cases.

One reason is that solid tumors lack clear target markers for CAR-T cells.

"Blood cancers are relatively straightforward. They’re made up of fairly uniform cells, so most of them express the same target molecule. Introducing CAR-T cells that target that molecule allows them to wipe out most cancer cells. Solid tumors, though, are far more complex. Not all their cells express the same target molecules. Even if you go after one, cells expressing different molecules will survive."

On top of that, solid tumors are heavily fortified, making it extremely difficult for T cells to infiltrate.

"Blood is made up of immune cells called lymphocytes, so for T cells, fighting blood cancer is like battling on home turf. Solid tumors, by contrast, are shielded by a tumor microenvironment that includes fibroblasts, macrophages, and other cells that actively support cancer growth. To develop effective immune cell therapy against solid tumors, we need to find a way to breach those defenses."

Prof. Kagoya and his team are also engaged in forward-looking research aimed at making CAR-T cell therapy more widely accessible. Specifically, they are conducting research and development on “universal CAR-T cell therapy.”

Current CAR-T cell therapy is completely personalized, requiring immune cells collected from each patient to be individually processed and expanded, making the treatment both time-consuming and extremely costly.

At present, a single treatment can cost tens of millions of yen, limiting access to only a small number of patients.

The universal CAR-T cell therapy being developed by Prof. Kagoya involves producing large quantities of CAR-T cells from T cells collected from healthy donors, stockpiling them, and making them readily available for use in any patient at any time. If realized, this would dramatically reduce costs and make treatment far more accessible.

Using someone else’s cells, of course, triggers rejection. The challenge is creating cells that avoid rejection while still delivering reliable therapeutic effects.

"Worldwide, research is advancing toward universal immune cell therapy, including efforts to solve the rejection problem. The economic potential is enormous, so pharmaceutical and biotech companies are pouring in, and large-scale clinical trials are already underway. We’re a small lab, but we plan to build carefully from basic research, drawing on the knowledge we’ve accumulated over the years."

Prof. Kagoya now heads a research laboratory, but after graduating from medical school, he spent several years as a practicing hematologist. He had been drawn to basic research since entering medical school, but it was his experience in hematology that ultimately set him on the path to becoming a researcher.

"In treating blood cancers, we perform bone marrow transplants. Even patients who barely respond to chemotherapy can sometimes be cured in one stroke through a transplant. Witnessing those results firsthand was what drew me into basic research."

Bone marrow transplantation—transplanting another person’s immune cells to attack leukemia—is itself a form of immune cell therapy. But whether a donor’s marrow will work for a given patient is unknown until the transplant is done. In contrast, CAR-T cell therapy and TCR (T-cell receptor)-T cell therapy can directly and precisely target clearly defined molecules.

"In the early 2010s, these therapies hadn’t yet reached clinical use, but trials were being conducted in rapid succession, and results were starting to emerge. At the time, there were very few researchers in Japan working in this field, so I decided to study in Canada and pursue my research there.”

During his time abroad, he worked on research aimed at improving therapeutic efficacy by incorporating cytokines, which are bioactive substances involved in T-cell activation, into CARs.

“When cancer cells and CAR-T cells are mixed together in a dish, the cancer cells are completely wiped out by the next day. The specificity is remarkable. They do not attack anything other than the cancer cells. Seeing that with my own eyes, I was struck by how powerful this approach truly is, and I became completely absorbed in the research."

Prof. Kagoya has led his laboratory at Keio University School of Medicine for three years now. One of its greatest strengths, he says, is just how easily people connect across disciplines.

The basic research labs are all housed together in the Center for Integrated Medical Research, so it’s easy to get in touch with anyone. Being able to have casual conversations with researchers doing world-class work is something I'm truly grateful for. The same is true of our relationships with clinicians. In addition to providing clinical specimens such as patients’ cancer cells with informed consent, Keio clinicians are also well versed in basic research, allowing clinical and basic science teams to collaborate closely while exchanging ideas.”

To those considering the Keio University School of Medicine and a career in basic research, he offers this advice: "Find out what kinds of research are out there, and stay curious about the world beyond medicine, too."

"We share what our lab does on our website, and most researchers these days are doing the same. Reading about what researchers are doing can give you a real feel for what the School of Medicine is about, and might help you figure out what you want to pursue."

“And then there's the question of how to translate research into real-world treatments that reach patients. No matter how outstanding the research may be, major pharmaceutical companies will not automatically turn it into a drug. In some cases, researchers must establish startups, secure external funding, and further develop the technology themselves. A broad understanding of these business and economic aspects will serve you well down the road. I'm still learning as I go on that side of things myself.”

"What I'm ultimately aiming for is translational research, bridging the gap between basic science and clinical practice. The basic research I worked on during my time abroad is now being used in clinical trials involving patients. To see that happening, as both a physician and a researcher, is deeply moving. It's the most rewarding part of what I do."

For Prof. Kagoya, the research can't end at the bench. He works tirelessly to advance basic science while building collaborations with companies and research institutions and securing funding, all to bring treatments to patients. 

Behind it all is one unshakeable belief: a therapy capable of curing cancer must make it to patients.

Yuki Kagoya

Professor, Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine

Yuki Kagoya graduated from the University of Tokyo Faculty of Medicine in 2007 and completed a doctoral program (Doctor of Medical Sciences) in internal medicine at its Graduate School of Medicine in 2013. After working in the Department of Hematology and Oncology at the University of Tokyo Hospital, he conducted basic research on cancer immunotherapy at Princess Margaret Cancer Centre in Toronto from 2014 to 2018. He subsequently served as a lecturer in the Department of Cell Therapy and Transplantation Medicine at the University of Tokyo Hospital, the director of the Division of Immune Response at Aichi Cancer Center, and an adjunct professor of Cellular Oncology at Nagoya University Graduate School of Medicine, before assuming his current position in January 2023.

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