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All in the Family

TAKAMI SATO, MD, PHD, AND RINO SEEDOR, MD ’15
Father-Daughter Team Works to Find Cure for Rare Cancer

Takami Sato, MD, PhD, came to the United States from Japan in 1991 to further his medical training in oncology. He intended to stay five years. He’s still here.

Sato, the K. Hasumi, MD, Professor of Medical Oncology and research director of the Metastatic Uveal Melanoma Program at Jefferson, is one of the country’s leading experts in uveal melanoma — a rare eye cancer that spreads to the liver, where it is always fatal.

He has dedicated his life to treating patients and conducting research into metastatic melanoma, and he leads the Melanoma Research Institute of Excellence (MRIE) — one of very few institutions in the nation dedicated to research on uveal melanoma prevention, diagnosis, and treatment.

Combining two internationally recognized specialties within Jefferson’s National Cancer Institute-designated Sidney Kimmel Comprehensive Cancer Center — uveal melanoma and skin melanoma — the MRIE is led by some of the foremost experts in the field, including Andrew E. Aplin, PhD, deputy director of the Sidney Kimmel Comprehensive Cancer Center, and postgraduate alumna Marlana Orloff, MD, RES ’12, FEL ’15, the Alexander and Johnston Family Endowed Clinical Director in Uveal Melanoma.

And now, Sato’s daughter, alumna Rino Seedor, MD ’15, has joined the team. Seedor is following in her father’s footsteps as a medical oncologist and research scientist focused on the prevention and treatment of uveal melanoma.

Like Father, Like Daughter

Neither Sato nor Seedor set out to become uveal melanoma specialists.

In fact, Sato didn’t even start out planning to settle in the United States.

After graduating from Jichi Medical University in Japan, Sato — then a pediatric oncologist — decided to continue training in the U.S. through the Noguchi Medical Research Institute, which provides clinical study abroad programs.

It was there he met two men he considers mentors: Jefferson’s Michael J. Mastrangelo, MD, who was a professor of medicine and medical oncology and a former director of both the Division of Medical Oncology and the Solid Tumor Service, and Joseph S. Gonnella, MD, former dean of the medical college.

“Dr. Gonnella asked what I wanted to do. I mentioned I was interested in cancer immunotherapy, then he connected me to Dr. Mastrangelo, who was doing a cancer vaccine trial,” Sato says.

At the time, Mastrangelo was seeing uveal melanoma patients whose cancer had metastasized to the liver. Sato’s experience conducting abdominal ultrasounds made him a good candidate to join the team.

During that time, Sato spent several years in the laboratory of David Berd, MD ’68, investigating the method of stimulating patients’ immune systems with their own cancer cells modified with a chemical called DNP. The vaccine with DNP-modified cancer cells showed promise in slowing the progression of metastatic uveal melanoma. The work became part of Sato’s doctoral thesis.

Ongoing discussions with Mastrangelo led to possible treatments for metastatic uveal melanoma. Since traditional systemic chemotherapy didn’t seem to work for liver metastases, they focused on liver-directed chemoembolization in 1995.

Chemoembolization involves injecting a mixture of chemotherapy drugs and oily contrast into the hepatic arteries to kill cancer cells and, at the same time, block the vessels supplying blood to the tumor with gelatin sponge embolic materials, thereby cutting off its supply.

The treatment was effective, but not effective enough. Because of Mastrangelo’s background in tumor immunology, the pair decided to try another therapy — “one that would mess up the cancer microenvironment in the liver,” Sato explains.

In 2000, they turned their focus to dendritic cells, which can uptake cancer antigens and prime T cells to attack cancer cells. Their idea was to create a vaccine in the liver tumor site using granulocyte-macrophage colony-stimulating factor (GM-CSF) — a protein cytokine that plays a crucial role in the production and regulation of white blood cells — to stimulate the patient’s immune system to recognize and destroy cancer cells.

“So, we kill the cancer cell by stopping blood flow — that is embolization — and we add the GM-CSF to let the cancer antigens taken up by the dendritic cells stimulate systemic immunity,” he says. “We started the first-in-human immunoembolization clinical trial in collaboration with Dr. Kevin Sullivan, an interventional radiologist at Thomas Jefferson University Hospital. We now have treated more than 600 patients whose liver metastases were treated with immunoembolization over the past 25 years.”

When Sato first arrived at the program, the median survival rate for a patient with metastatic uveal melanoma was four to five months; currently, the median survival rate has increased to about 22 months. Sato emphasizes that this is the result of teamwork.

“We have developed a unique multidisciplinary clinical program for metastatic uveal melanoma that includes medical oncologists, interventional radiologists, and radiation oncologists,” he says. “Close communication with ocular oncologists Drs. Carol Shields and Sara Lally (SKMC ’01) at Wills Eye Hospital is also critically important for comprehensive care of uveal melanoma patients.”

The increase in survival rate is good, he says, “but not good enough. That’s the reason why we keep working.”

While Sato says he didn’t plan to spend his career in the field of uveal melanoma, it quickly became his life’s work. And somewhere along the line, it became his daughter’s as well.

“It’s not something I planned on — it all just fell into place as the years went by,” Seedor says.

While Seedor was exposed to the world of medicine throughout her childhood, she didn’t think early on, “Oh, I definitely want to be a doctor,” she says.

In high school, she signed up for a class called Medical Careers that placed students in hospitals to shadow medical personnel. She enjoyed the class and inched a little closer to choosing a career in medicine. In college, she inched even closer.

By medical school she was leaving her options open — oncology was a possibility. Then it became a probability. Then a reality. But still, she didn’t really consider uveal melanoma as a specialty.

“I actually thought I’d never want to do something like what my father does — something so specialized and niche,” she says. That changed after a few rotations at Jefferson and working on several uveal melanoma projects during fellowship.

“As I became more mature and understood the different oncologic specialties, the uniqueness of uveal melanoma, how rare it is, how aggressive it is, and how few treatments there really are, I became more appreciative of all of the time and dedication my father has put over the past 30-plus years into this rare cancer — how much improvement there has been, and how much more there is to discover,” she says.

“I became more and more interested, and I saw myself being part of the team that carries on his legacy and work.”

While their work intersects, it doesn’t exactly follow identical routes.

“We work on similar clinical trials together, but one of the projects I’ve worked on is the geospatial analysis of uveal melanoma patients,” she says.

Uveal melanoma is a rare cancer with an incidence of about five to six people per every one million in the United States. However, Sato and Orloff noticed an unusually high number of patients with the disease coming from similar areas in North Carolina, Alabama, and New York.

To investigate further, Seedor applied for and received a pilot award from the MRIE to study the clusters and determine if there were more across the country. The information could potentially help find the cause behind the disease and determine what can be done to prevent it.

Dreams and Visions

The MRIE had been Sato’s dream for 10 years before it became a reality in 2022. Established with a generous gift from an anonymous grateful patient and family, the institute built on an existing program that continually produced innovative research and new treatments at Jefferson.

“Achievement made by one person is limited,” he says, adding that organizing through an institute gives more power to the effort and allows for better teamwork among researchers, clinicians, and patient advocacy groups.

While Sato has been immersed in uveal melanoma for more than three decades, Seedor’s work is just beginning. It’s work that isn’t easy, but there is a lot of motivation — both professional and personal — that keeps them going.

A doctor feels happy if the patient is cured. But this disease is so difficult, and a cure is not frequently seen, so the next incentive, the next motivation, is trust ... and hope. Hope for finding better treatments for the future. That’s a very important thing to continue working on.

Takami Sato, MD, PhD

“A doctor feels happy if the patient is cured. But this disease is so difficult, and a cure is not frequently seen, so the next incentive, the next motivation, is trust,” Sato says. Working together with patients and their families with compassion as they move through the stages of the disease inspires him.

“And hope,” he adds. “Hope for finding better treatments for the future. That’s a very important thing to continue working on.”

Seedor says she too is inspired to keep doing the work because of the hope for better treatment. “There’s the hope that we’re the ones who are going to find it, and that keeps us going.”

She admits that caring for patients with such bleak prognoses is difficult.

“It’s especially hard for me when I meet a younger patient with young children like myself,” says Seedor, who has two young sons. “But someone has to do it. Someone has to walk these patients from their diagnosis through treatment until the end. And I want to be that person for them.”

Other motivation comes in the form of patient support, as the MRIE is run solely on philanthropy. Much of the research into uveal melanoma is funded through government and private grants; however, the MRIE itself relies completely on private donations.

“Government funding from places like the NIH supports scientific research, not the infrastructure of the MRIE,” Sato explains. “Scientific discovery is important, but it doesn’t immediately benefit the patients.”

Developing a strategic plan to improve patients’ lives, determining a course of treatment, and supporting them throughout the process is part of the overall mission of the MRIE. The institute also conducts information sessions to keep patients and their families informed of the latest research, therapies, and clinical trials.

The ultimate goal of the MRIE is to advance patient care, support basic science and research, and continue to conduct clinical trials that could offer better treatments for the disease, Sato says.

Seedor says she admires her father’s unwavering devotion and perseverance that made his vision for the MRIE a reality.

“I’ve watched my father work really hard all my life, and now I’m able to understand why he works hard and what comes of his hard work and all the years of dedication,” Seedor says. “I think it’s very unique to see and to be able to continue that work in my career. That’s very special.”

She says the biggest lesson she has learned from her father is that “hard work eventually pays off.” Another lesson is to continually ask “why.”

“He’s always asking why. Why did a patient progress? Why did they recur so quickly? Why, why, why? That inquisitiveness is what drives understanding of a cancer — how to better treat it, how to further the research field,” she says.

For Sato and Seedor, Jefferson is a “second home” — not only because they spend so much time there, but because several family members have a connection to the institution.

Indeed, for the Sato family, the combination of science, medicine, and Jefferson is a family affair. Seedor’s husband, Brett Seedor, is an inpatient oncology nurse at Jefferson. Sato’s oldest son, Takahiro Sato, PhD ’13, earned his doctorate in molecular pharmacology and structural biology from Jefferson College of Graduate Studies in 2013, and his son’s wife, Crystal Sato, PhD ’16, received her doctorate in cell and developmental biology in 2016. A younger son, Shingo Sato, is a clinical research coordinator as well as an AI specialist. He serves as associate program manager and director of database design and utilization at the MRIE.

Sato says he is grateful to Jefferson for giving him a home and helping him realize so many dreams — from accepting him as a young doctor and receiving invaluable mentorship from Gonnella and Mastrangelo to supporting his research and the creation of the MRIE.

“At the beginning, I was going to go back to Japan in five years, but after five years, I found out I didn’t finish my project. And then the next five years, more projects ... and then more … I couldn’t move because this is a never-ending project,” he says, laughing.

But he says he is aware that his time is limited, and he hopes the next generation will continue his work.

“I hope Dr. Orloff and Dr. Seedor will continue to strengthen the institute to help patients with melanoma,” he says. “That is my dream.”

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