Advancing Penn’s ImmunoRevolution to Myeloma

Pushing science forward takes teamwork, and at Penn Medicine, Alfred Garfall, MD, has found that in spades — from working with colleagues who share his passion for patients and research, to finding partners — including his 10-year-old son, Alex — to ride alongside in the Breakthrough Bike Challenge (BBC), an annual fundraiser to support cancer research at the Abramson Cancer Center.

As a physician-scientist and assistant professor of Medicine at the Perelman School of Medicine, Garfall has discovered that philanthropy, no matter the size, can be an indispensable player. He’s received support from grassroots-style fundraisers that rely on a collective community to make an impact, including $30,000 from the BBC that helped launch a very promising project.

Alfred and Alex Garfall
Alfred Garfall, MD, and his son, Alex

Garfall focuses on multiple myeloma, a blood cancer that affects plasma cells found in bone marrow. Each year, about 30,000 Americans are diagnosed. “The problem with myeloma is relapse,” says Garfall, who studied biology as an undergraduate at Princeton and attended medical school at New York University. “We have really good therapies that can kill the myeloma cells, but eventually the cells are likely to grow back with resistance to therapy.”

A South Jersey native and father of two, Garfall first came to Penn for a hematology/oncology fellowship in 2011, during the run up to what has become known as the ImmunoRevolution: the institution’s all-out pursuit of novel ways to use CAR T cell and other immunotherapy approaches to cure cancer and myriad other diseases. It was sparked by Penn’s renowned immunologist/oncologist Carl June, MD, director of the Center for Cellular Immunothera¬pies, whose team’s first success came in a CAR T cell therapy that showed long-lasting remissions in children and adults with B-cell acute lymphoblastic leukemia and was the first FDA-approved therapy of its kind.

Two years ago, Garfall launched an immunotherapy study thanks to the BBC support. As a result, his team was able to gather promising, early-stage data — enough to attract a $275,000 award from the National Institutes of Health to continue the investigation.

A Germ of an Idea Ready for Seed Funding

Study process

With the support of both June and of his mentor, Edward Stadtmauer, MD, chief of hematologic malignancies, Garfall started a clinical trial to test CART-19, the therapy June’s team had its first success with in B-cell leukemia, in myeloma patients: a first for the disease.

The results were illuminating. “We had this one patient who was dying of myeloma, for whom nothing whatsoever was working,” Garfall says. “Now six years later, she’s disease free, but she was also the only one who did that well — and I wanted to know why.”

They found that her immune system had developed an exceptional response to SOX2, a protein that gives embryonic stem cells the ability to grow an entire human being from one cell. Dr. Garfall knew the finding might be significant; a connection between immune responses to SOX2 and the development of myeloma had been established years before.

“Perhaps she did so well because CART-19 created new anti-SOX2 immune responses and those may be keeping her in remission,” Garfall says.

Now the question became “can we replicate that outcome for other patients?” Garfall was in the right place to find out.

Inspired and Supported by Penn’s Immunology Leaders

headshot of Gerald and Beatriz
Gerald Linette, MD, PhD, and Beatriz Carreno, PhD


headshot of Sandra Susanibar
Sandra Susanibar Adaniya, MD

“As I was thinking about this idea, I was surrounded by colleagues in our Center for Cellular Immunotherapies, hearing their stories about bridging clinical observations and the lab, chasing down remarkable findings and trying to figure out what’s going on in their patients,” Garfall says.

Inspired by the community’s “dogged curiosity,” Garfall reached out to Gerald Linette, MD, PhD, who, along with his partner, Beatriz Carreno, PhD, heads a lab focused on cancer immunology research. “Even though I hadn’t met or worked with Gerry and Beatriz before, their lab is just a few floors below my office and in the same building as the patient clinic — so we’re set up to collaborate in a really special way to make advances for patients,” Garfall says.

Linette suggested they try to isolate the T cell receptors responsible for bringing on the SOX2 response and potentially turn it into a therapy for other patients. By finding the genetic sequence of T cells that recognize SOX2, they can re-engineer any patient’s T cells into ones that mimic that response.

Currently, with the help of patients who donate their T cells, the Linette/Carreno lab is providing the expertise for the collection and re-engineering of T cell receptors. Hematology/oncology fellow Sandra Susanibar Adaniya, MD, has worked with Garfall and the Linette/Carreno lab to push the project forward, recruiting patient volunteers in the clinic and working in the lab to isolate and characterize their T cells that recognize SOX2.

Everyone Can Be a Partner in Progress

If all goes well, a clinical trial will begin, and Garfall hopes that results will be published in a few years. In the meantime, he realizes his good fortune in getting his project off the ground with a grant from the Breakthrough Bike Challenge, which this year was held virtually due to COVID-19. In the spirit of paying it forward, Garfall and his son pedaled 100 miles last summer for the cause, joining nearly 500 fellow bikers, spinners, runners, and walkers who logged 20,875 miles in all.

The event raised an impressive $275,000, with an average donation of just over $115. But as Garfall knows from his experience two years ago, every penny counts for early investigator projects. Although this year’s BBC funds have not yet been disbursed, 2019 monies have helped support three prostate cancer studies.

“Potential donors to research may think: These projects take so much money, how could I possibly make a difference?” Garfall says. “But the key is that the effect multiplies. That seed funding, even if it’s modest, enables us to get larger amounts from outside sources.”

Breakthrough bike challenge graph

The BBC funding, he says, did exactly what pilot grants are designed to do — provide the spark to launch projects on the path toward discoveries and cures. “You can have a lot of good ideas but if you can’t put together a team and do the initial experiments that will attract outside resources, your projects won’t get going.”

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