Immunology Offers Hope for Melanoma Patients

By Cathy Clark, APR - January 19, 2021

Moffitt Cancer Center President and CEO Dr. Patrick Hwu knows the value of creative collaboration and partnerships in his work as a physician-scientist.

Describing his early years, he says he was fortunate to have worked with Steven Rosenberg, MD, PhD, using immunotherapy to treat patients at the National Cancer Institute, early in his career. Rosenberg pioneered the development of effective immunotherapies and gene therapies for patients with advanced cancers. Hwu completed a fellowship in Medical Oncology and Immunology at the NCI from 1989 to 1993.

“T cells [an essential part of the immune system] naturally grow against melanoma,” said Hwu. “If you place melanoma cells in a culture dish and add a growth factor called interleukin-2, the T cells naturally grow out that recognize melanoma. You can then give those cells back to the patient to kill the tumor.” Hwu, working with Rosenberg, routinely used this tumor-infiltrating lymphocyte therapy to treat patients.

The work using TIL showed success in patients with melanoma, but not all cancers. “We were frustrated because we couldn’t do this with other kinds of cancers, very common cancers like colon, breast and ovarian,” said Hwu.

Hwu and his colleagues with Rosenberg’s group were looking at ways to train immune cells to recognize the tumors. He began working with world-renowned immunologist Professor Zelig Eshhar of Israel’s Weizmann Institute of Science, who was doing a sabbatical at the NIH.

“This was in the early 1990s, at which time I was on a separate project putting genes into T cells. Zelig had devised a method of putting antibody genes with signaling genes in immune cells to redirect different cells, but he hadn’t done it in primary T cells.” They worked together, initially focusing on genetically engineered T cells for three kinds of cancers.

A New CAR Takes Off

The team used chimeric receptor genes against ovarian, colon and breast cancers. The only one that worked robustly was the one against ovarian cancer, so they pursued that one with a clinical trial, which resulted in the first CAR T against cancer. Their findings suggested the strategy may allow new approaches toward the adoptive immunotherapy of cancer in humans. The team, including Hwu, Eshhar and Rosenberg, published their first paper focused on CAR T in the Journal of Experimental Medicine in 1993, with Hwu as the lead author and Eshhar the senior author. “Now, this work is refined, and it is known exactly which optimal genes and which signaling areas to use. But we were barely able to get genes in the T cells at that time in the early 1990s,” said Hwu.

Over the following years, Hwu published more than 300 clinical and scientific research papers in prestigious medical-scientific journals, the likes of Nature Medicine, Blood and The New England Journal of Medicine, along with invited articles, editorials, book chapters, manuals and other teaching publications. His name appears on more than a dozen U.S. patents related to adoptive immunotherapy and targeted treatment of cancer; he has served as principal investigator on even more clinical trials focused on immunotherapy.

An Early Connection

Hwu’s relationship with Moffitt Cancer Center goes back to Moffitt’s early days. He recalls coming to Tampa to deliver a Grand Rounds lecture around the time when Moffitt had earned its status as an NCI Comprehensive Cancer Center. He had been invited by Julie Djeu, PhD, former chair of the Immunology Department, known for her pioneering work in helping identify the role of natural killer cells in activating the immune system to kill tumor cells.

“It was a great experience, and I remember Julie telling me stories of when they started doing research at the early days of Moffitt. It’s really interesting because the place had risen so fast,” said Hwu. “I remember remarking to myself back then how impressed I was at how fast that the center had grown from zero to comprehensive cancer center status.”

Hwu has been a member of Moffitt’s Scientific Advisory Board since 2012, and he has served on advisory boards to numerous other cancer centers during his career.

“I feel like I am doing a service to other cancer centers because, in the end, we’re not competing. We’re just trying to treat cancer because the only goal is to try to come up quicker with a cure and have patients have good outcomes now and better outcomes in the future,” said Hwu.

Research Is Key to Better Therapies

Upon his arrival, Hwu will see patients with melanoma in the clinic and also will do collaborative research in T-cell therapy. The aim is to make the cells more potent, which will enable treatment with fewer cells, thus decreasing the cost of the therapy and making it more scalable and more effective.

portrait of blockquote author

"Research could absolutely lead to better therapies for patients."

- Dr. Patrick Hwu

One thing Hwu would like people to know is the importance of research. “Research could absolutely lead to better therapies for patients. Our goal must be to give the patients the best care today, but we also have to continually improve that. Because as long as 600,000 people are dying in this country of cancer every year, 45,000 in the state of Florida, we’ve got to change that, and research can change that.”

He cited examples of using CAR T cells to treat patients with lymphoma and how immunotherapy has helped cure many of these patients. Targeted therapy and immunotherapy are offering hope to patients with melanoma. “People used to say, ‘How can you take care of melanoma patients? Isn’t that depressing?’ And this was said throughout much of my career,” said Hwu. “But now, over the last five years, all the science has caught up and been translated to the clinic, and patients are doing very, very well. Patients who absolutely would have passed away quickly 10 years ago, 15 years ago, are being essentially cured and living a long life with their families, which is what we want. A durable survival, that’s what we really want and it’s through research.”

In addition to coming up with novel agents to treat cancer, Hwu believes that prevention is another important area. “We have a very strong Population Science group because, in the end, the best way to treat cancer is to not get it or to catch it early,” said Hwu. “That’s probably going to be the most impactful in the long run, and a requirement of a comprehensive cancer center is to look at things that involve prevention. How the institution is affecting what we call the catchment area is very important, how we are going out and serving the people in our catchment area.”

Hwu’s vision: To make the most impact on helping cancer patients survive, to decrease cancer-related deaths, and to have Moffitt be the group that makes the most impact. “There are a lot of areas along the way that we’re going to focus on to accomplish this.”

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Cathy Clark, APR Senior Managing Editor More Articles

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