Penn’s Carl June splits a $3 million Breakthrough Prize for pioneering the cancer treatment CAR-T

University of Pennsylvania cancer scientist Carl June is sharing a $3 million Breakthrough Prize for discovering how to attack cancer by harnessing the patient’s immune system, award sponsors announced Thursday.

Versions of the genetic engineering technique that he pioneered 13 years ago at Penn, nicknamed CAR-T, have now been used to treat more than 20,000 patients with leukemia and other deadly blood cancers, with success rates ranging from 50% to 90%.

June is splitting the award with Michel Sadelain, who developed a similar approach at Memorial Sloan Kettering Cancer Center in New York.

The pair will be honored at an April 13 ceremony in Los Angeles along with the winners of four other Breakthrough Prizes, annual awards given in the sciences and math by a group of prominent tech-industry titans.

In an interview, June said he appreciated the prize — the most lucrative of many he has won — yet is even more enthusiastic about what it represents.

In the mid-1990s, he and Sadelain were among a handful of scientists trying to enhance the power of patients’ immune-system agents called T-cells (the “T” in the abbreviation CAR-T).

Once their work started to show promise, hundreds of academic laboratories and companies jumped into the fray. June’s lab developed the treatment that became the Novartis drug Kymriah, approved by the FDA in 2017, and five other CAR-T drugs have come on the market since then.

“To me, that’s the most rewarding thing, to be able to see something go global like this, and to see so many people benefit,” he said.

June, who came to Penn in 1999, is now among many trying to engineer these T-cells to fight other kinds of cancer, the solid tumors that account for most cases of the disease. He also is studying whether the concept might work against noncancerous diseases, among them heart failure and autoimmune conditions such as lupus.

To tackle those challenges, June is trying to marry the CAR-T approach with another hot technology to emerge recently from Penn: the messenger RNA molecules that form the basis of the Pfizer and Moderna vaccines against COVID-19. Among his partners on that research is a past winner of the Breakthrough Prize, Penn mRNA scientist Drew Weissman.

But if not for a series of fortuitous events dating back to the Vietnam War, June might never have become a cancer pioneer. In 1971, he was planning to enroll at Stanford University, but instead he was drafted and sent to the U.S. Naval Academy.

“I thought I was going to be on submarines,” he said.

Yet the war had ended by the time June graduated from Annapolis. Needing physicians, the Navy paid for his medical school at Baylor College of Medicine, encouraging him to focus on malaria and other infectious diseases. That expertise eventually led to his first attempts at engineering T-cells in the mid-1990s — not to fight cancer, but HIV.

These early tailored T-cells were ineffective against HIV, but June and his colleagues discovered that they nevertheless had a useful property: they persisted in patients’ bodies for years. With additional tweaks, these early efforts paved the way for future generations of CAR-T cells that eventually would prove potent against cancer.

Here’s how it works: A patient’s T-cells are removed from the body, genetically engineered to act as customized cancer-fighters, then reinfused into the body.

The first successful test came in 2010, 11 years after June came to Penn, on two adult cancer patients whose disease had not responded to traditional treatments.

Both had chronic lymphocytic leukemia, a type of cancer that affects another agent of the immune system called B-cells. So in treating the two men with CAR-T, June and his colleagues were tweaking a healthy arm of the immune system, T-cells, to attack another that was riddled with cancer.

Two years later, at nearby Children’s Hospital of Philadelphia, they used the approach to treat 6-year-old Emily Whitehead, who had a different type of leukemia. She almost did not survive the treatment, as it stimulated an overreaction by her immune system, with a dangerously high fever and elevated levels of an inflammatory signal called IL-6.

But once again, June’s path to success as a cancer pioneer was marked by serendipity.

By coincidence, June’s own daughter had a form of pediatric arthritis that caused her to have elevated levels of IL-6, the same inflammatory molecule that was overtaking Whitehead’s immune system.

June knew the FDA had just approved a new drug to treat that problem in arthritis patients. Might it help Whitehead, too? He called up the physicians who were taking care of the 6-year-old in CHOP’s intensive care unit, to ask if they would give her the drug.

“They said I was a cowboy for suggesting that,” he recalled in a 2018 TEDMED talk.

But they did, and Whitehead got better. And this fall, she enrolled as an undergraduate at the place where Carl June developed her treatment: the University of Pennsylvania.

“It’s really completed the circle,” he said.

Penn scientists have won a Breakthrough Prize on three previous occasions. Weissman, the mRNA scientist, split his prize with Katalin Karikó in 2022. Virginia M.-Y. Lee won a 2020 Breakthrough Prize for her research on Alzheimer’s and other neurodegenerative diseases. Charles Kane and Eugene Mele won the prize in physics the year before that, honored for their study of high-tech materials called topological insulators.

Yuri Milner, one of the prize sponsors, also has a Penn connection. The prominent tech investor attended Penn’s Wharton School from 1990 to 1992.

He and his wife, Julia, established the Breakthrough Prize in 2012, along with Google cofounder Sergey Brin; Facebook cofounder Mark Zuckerberg and his wife, physician-philanthropist Priscilla Chan; and 23andMe founder Anne Wojcicki.

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