An Interview with Carl June, MD, a Pioneer in CAR T-cell Therapy
In 2012, Carl June, MD, a pioneer in the development of chimeric antigen receptor (CAR) T-cell therapy, helped treat Emily Whitehead, the first child to receive CAR T-cell therapy on an experimental basis. The therapy put Emily’s acute lymphoblastic leukemia (ALL) into remission. Today, Emily is a healthy teenager, and two CAR T-cell therapies are approved for use by the U.S. Food and Drug Administration (FDA) for several types of lymphoma in adults and ALL in pediatric patients whose cancer has not responded to other treatments. CAR T-cell therapies are being further tested in preclinical and clinical studies to evaluate their efficacy in treating solid tumors, HIV, and autoimmunity.
The road to FDA approval was not always smooth. CAR T-cell therapy is prohibitively expensive, often topping $1 million when all associated costs are considered. It does not work for every patient, although when it is successful, a single dose of therapy can elicit complete response. Some patients who receive the therapy, including Emily, undergo a punishing side effect: cytokine release syndrome, also known as a cytokine storm. The cytokine storm is a hyperactive response by the immune system, sparking high fevers, swelling, and sometimes, death.
When Emily developed the cytokine storm, June speculated that tocilizumab, a drug originally designed to treat rheumatoid arthritis, might stop it. That unprecedented decision saved her life, and later became a standard treatment for cytokine release syndrome. In a curious intersection of diseases, cytokine storm emerged this year as a complication of COVID-19. June, a professor in immunotherapy at the Perelman School of Medicine at the University of Pennsylvania, recovered from his own bout with COVID-19 and is now exploring ways to improve treatment of the disease.
June recently spoke with Tanya Bondar, PhD, deputy editor of Blood Cancer Discovery, a journal of the American Association for Cancer Research (AACR). The full interview is available on the journal’s website. Here, some additional highlights from his conversation with Bondar.
The face of CAR T-cell therapy
Unsurprisingly, Emily Whitehead’s story touched and inspired countless people. June is in frequent contact with her and her parents, and delights in pictures that have captured her growing up. The Whiteheads started a foundation that supports CAR T-cell therapies, recently contributing $125,000 to Stand Up To Cancer, for which the AACR is the Scientific Partner.
June feels that beyond being the face of a groundbreaking new therapy, Emily helped the public—and the government agencies that fund medical research—understand the importance of investing in science.
“Right now, because of COVID-19, everyone understands the importance of science,” he told Bondar. “Before, that fell on deaf ears. We all tried to lobby, to make Congress understand why they needed to fund medical research. What finally helped was some of our patients, like Emily Whitehead. She really helped people understand and appreciate that CAR-T therapy could save lives.”
CAR T-cell therapy poised for growth
The FDA approved the first immune checkpoint inhibitor, ipilimumab, in March 2011, and the first CAR T-cell therapy in August 2017. Today, the FDA has approved seven checkpoint inhibitors for a wide range of cancer types. June said that based on the time gap between checkpoint inhibitors and CAR-T cell therapy, he anticipates rapid growth for CAR-T in the next few years.
“I think we can look forward to CAR T-cell therapy taking that same sort of trajectory,” June said, noting that there are currently at least 500 CAR T-cell therapy trials listed on clinicaltrials.gov. “It’s on the same exponential upswing.”
June noted that CAR T-cell therapy has not been introduced in lower- or middle-income countries, due in part to poorer infrastructure and a lack of physicians trained to administer the treatment. June said he is involved in projects in Costa Rica and India that would train people to manufacture CAR T cells and teach medical professionals to care for the patients who receive them.
Bondar asked June if CAR T cells might someday be manufactured in mass amounts. “I’m positive that it will be done,” June told her, adding that reagents and equipment needed to make the cells will someday be more readily available. “I promise you that the cell engineering in a box is doable.”
COVID-19: The personal and the professional experience
June has publicly discussed his experience suffering from COVID-19. He said his illness began with respiratory symptoms. He later developed swollen lymph nodes and gastrointestinal problems. While he was recovering at home, he voraciously read journal articles about the virus, and eventually began to feel better.
“This lasted for six weeks, and I’m in good health otherwise,” he told Bondar.
June also discussed the chilling effect the pandemic has had on the scientific research community. When the coronavirus was at its peak in Philadelphia, some functions in his lab were limited, slowing the research process. “There’s an Achilles’ heel,” he said. “For us to do our phase I trials, you need biopsies, and the biopsies need to be able to get processed … all the things that I needed to analyze them closed down.”
June expressed concern that the pandemic will lead to a reduction in funding for scientific research. “I want to make sure that we don’t lose people to science because of it,” he said.
June as a mentor
June’s hope of maintaining a robust pipeline of young scientists begins with his own lab. The competition for grants is always fierce, and may tighten in the current climate, but he intends to maintain a spirit of collaboration.
“If you have a good environment where people feel like sharing, you get much better progress than if you have a lot of people doing secret projects,” June told Bondar. “I’ve never let anyone have secret projects in the lab. Everyone is secure that whatever they work on, they know they’ll be protected. And if other people are independently work on the same thing, I make them work out compromises.”
Editor’s note: June is a member of the Editorial Board for Blood Cancer Discovery, the AACR’s latest journal.