A Q&A With Dr. Carl June
Dr. Carl June from the University of Pennsylvania is featured in MFF’s Superhuman Body as the researcher who, along with his team, saved the life of Emily Whitehead—a six-year-old with “incurable” leukemia, and the first pediatric CAR T-cell therapy patient. Thanks to Penn Medicine and Children’s Hospital of Philadelphia (CHOP), Emily not only would be cured, but also forever changed the world of cancer treatment.
We’ve collected a series of questions and answers—both from published interviews and our own conversations with Dr. June—that tell his personal story. We learn everything from how he helped develop CAR T therapy, to Emily’s brush with death, to Dr. June’s ideas about the future of cancer treatment and cures.
Is It Too Much to Hope for, or Are We Close to Curing Cancer?
DR. JUNE: Cancer has been around for thousands of years, but it’s only in the last fifty years that we’ve understood what causes cancer. If you understand why something’s broken, it’s easier to put it back together. And now, we have very specific therapies, some of which are completely personalized. So I’m really optimistic that this next generation is going to see the cure of cancer.[1]
Is It the Immune System’s Job to Attack Cancer?
DR. JUNE: The immune system didn’t evolve to fight cancer; it evolved to fight pathogens invading from the outside. Its job is to kill bacteria and viruses. For more than a century, researchers have been studying the immune system as a way to fight cancer, but cancer vaccines have been disappointing. They’ve only worked on cancers caused by viruses, such as cervical cancer or liver cancer.[2]
The reason the immune system has trouble with most cancers is that cancer doesn’t invade from the outside; it evolves from our own cells. So either the immune system doesn’t recognize the cancer as a problem, or it attacks both the cancer and our normal cells—leading to autoimmune diseases, like colitis or multiple sclerosis.[3]
So How Did You Turn the Immune System Into a Cancer-Killing Machine?
DR. JUNE: Well, CAR T cells are a way to personalize your own immune system—by creating a synthetic immune system designed to recognize and kill cancer cells. We started with naturally occurring parts of the immune system, white blood cells called T cells and B cells. T cells have evolved to kill cells infected with viruses, and B cells make antibodies that kill bacteria.[4]
We’ve learn a lot about those cells during AIDS and the recent COVID epidemic. I mean, those cells are the ones that respond to a vaccine, and evolved in our body to kill viruses like COVID and HIV.[5]
For CAR T, we wanted to combine T and B cells in a way to repurpose them to fight cancer—by inserting the genes for antibodies from B cells into T cells. We put a receptor into those T cells so that they would lock on to and recognize a patient’s leukemia cell and kill it.[6]
The result was a chimera, a fantastic fire-breathing creature from Greek mythology, with a lion’s head, a goat’s body, and a serpent’s tail. So the new cells were called “Chimeric Antigen Receptor T cells,” or CAR T cells. When CAR T cells see and bind to their tumor target, they act like supercharged killer T cells on steroids. They divide and multiply by the millions, then attack and kill the tumor.[7]
CAR T cells are the first living drug in medicine. They stay alive and on the job for years. This is the beginning of a new paradigm in medicine.[8]
Can You Manufacture Car T Cells?
DR. JUNE: The only source of T cells are the patients’ own T cells, unless patients have an identical twin. We had to learn to grow a patient’s own T cells, and we developed a robust platform for this in the 1990s.[9]
What Were the First Successes You Had With Car T?
DR. JUNE: With my colleagues at the University of Pennsylvania, Bruce Levine and Jim Riley, we began treating HIV patients who had AIDS that was resistant to treatment. In 1997, we first tested CAR T in these patients, and found that those CAR T cells survived in the patients for more than a decade. The treatment improved their immune system and decreased their viruses, but it didn’t cure them. So for the next decade, we made improvements to the CAR T cell design.[10]
And at That Time, a Family Story Made Cancer Even More Personal to You?
DR. JUNE: Yes. I trained as a leukemia specialist and we gave routine, very toxic therapies to patients. But it wasn’t until my wife got ovarian cancer and had these same very toxic therapies that I saw—from the other side of the bed—how awful they really were.[11]
My wife had many, many complications from the chemotherapy—including the usual, where her hair came out and I went with her to buy a wig. She also had many other complications, like infections and hundreds and hundreds of needle sticks to draw blood. But the worst thing you can imagine is called mucositis. You cannot eat or drink, can’t swallow. I saw that our “standard treatment” was really not what we would like to have—which is a non-toxic therapy.[12]
How Did This Experience Lead to Your Work in Leukemia?
DR. JUNE: My wife died in 2001, and that’s when I really got very dedicated with my laboratory, on learning how to use the immune system to deliver cancer therapy instead of the poisonous chemotherapy.[13]
By 2010, we began treating leukemia patients with CAR T. Just one CAR T cell can kill 1,000 tumor cells, and each one can divide and divide and divide—until the last tumor cell is gone. There was no precedent for this in cancer medicine.[14]
We first treated three patients with advanced chronic lymphocytic leukemia—a form of incurable leukemia that afflicts approximately 20,000 adults every year in the U.S. One of these patients had already made his funeral arrangements. Within days after his CAR T cells were infused, he had high fevers, multiple organ failures, and became comatose. We thought he was going to die, and he was given last rites. But twenty-eight days after the infusion, he woke up—and his cancer was gone. In fact, two of the three patients we treated had durable remissions; the third had a partial remission.[15]
And Then You Met Emily Whitehead….
DR. JUNE: Emily was the first child we treated for leukemia; she was six years old and very ill. She literally was at death’s door, with a very aggressive, incurable form of leukemia—acute lymphoblastic leukemia (ALL). She had gone through a series of chemotherapy and radiation treatments over several years, and her leukemia had always come back. In fact, it came back three times. There were no approved therapies left, because she’d had them all.[16]
When we infused her with the CAR T cells in April 2012, at first nothing happened. But within a few days, she got much worse. As our adult patient had in 2010, Emily went on life support for kidney failure, lung failure, and coma. But the CAR T cells were much more vigorous and violent in killing the immune cells than we had seen in our adult patients. That’s how Emily came to have a 106-degree fever, just from the dying leukemia cells. All of the staff in the intensive care unit thought she was going to die.[17]
We did all the standard blood tests for infections, but could not find an infectious cause for her fever. But we did find something very unusual in her blood—which had never been seen before in medicine. That was our ah-ha moment.[18]
How Did You Save Emily?
DR. JUNE: We found in the laboratory that a protein called interleukin-6 (IL-6) was over 1,000 times above normal in Emily’s blood. By sheer coincidence, IL-6 turned out to be the protein that had caused my daughter’s arthritis—so as a cancer doc, I’d been following experimental arthritis therapies for her. Just months before Emily was admitted to the hospital, a new arthritis therapy called tocilizumab had been approved by the FDA to treat elevated levels of IL-6, and the drug had just been added to the pharmacy at Emily’s hospital. I called her doctors in the ICU and said, “Why don’t you treat her with this arthritis drug?” They said I was a cowboy for suggesting this, but then her doctor quickly asked permission to the institutional review board, her parents—and everybody, of course, said yes. It had never been given to a cancer patient before, but we gave it to her right away.[19]
By the next day, there was a remarkable, miraculous recovery. And twenty-three days after her treatment, Emily was declared cancer-free. She was discharged just after her 7th birthday—and we’ve seen her grow up into a young woman. Now, it’s a joy to see her looking toward college.[20]
Both Emily and Your Adult Leukemia Patients Experienced an Intense Response to Car T. Is That Normal?
DR. JUNE: Yes. Now we have a name for this violent reaction—the high fevers and coma following CAR T treatment; we call that cytokine release syndrome, or CRS. We’ve found that it occurs in nearly all patients who respond to the therapy—but it does not happen in those patients who fail to respond. So paradoxically, our patients now hope for these high fevers after therapy. And when the FDA approved CAR T cells for leukemia, they also co-approved the use of tocilizumab to block the IL-6 effects and the accompanying CRS in these patients. That was a very unusual event in medical history.[21]
How Successful Is Car T?
DR. JUNE: In a study at CHOP, we saw a 90 percent complete remission rate in patients with advanced cancer, which is unheard of in more than fifty years of cancer research. In fact, companies often declare success in a cancer trial if 15 percent of the patients had a complete response rate.[22]
In a ten-year look-back—not just for Emily, but for other patients too—we can now say confidently that they’ve been cured of leukemia. We didn’t know that initially, because these patients always had multiple relapses after chemotherapy and radiation and bone marrow transplants. But most of the people treated with CAR T cells for acute leukemia have had durable remissions, which is very exciting and pretty much unheard of for refractive cancer therapies.[23]
CAR T actually is a living drug. CAR T cells have persisted and remain in these patients’ blood, ten years after a single infusion. And those cells remain effective.[24]
How Have These Successes Impacted Today’s Treatments of Cancer?
DR. JUNE: When we began treating Emily in 2012, there was no industry for CAR T cell therapies. There was only a handful of academic laboratories in the world attempting to do this. So it was very experimental. The first FDA approval for the treatment we used on her was in 2017. The field has seen tremendous progress since then.[25]
For example, Emily had had three relapses. There are trials now to move CAR T up front—to allow doctors to use it earlier in a patient’s treatment, so as to minimize the amount of chemotherapy patients get. But we still have to wait until those trials occur. Plus, there are now several different FDA approved indications, including leukemia, lymphoma, and multiple myeloma, the most common blood cancer.[26]
My main interest now is to expand beyond blood cancer. There are hundreds of trials around the world testing CAR T cells in nearly every cancer you can think of. The major scientific challenge is making these cell therapies—which work very well in blood cancers—to work in solid cancers, which are the more common tumors. And researchers are exploring treatment for cardiac damage, to enhance healing and regeneration, and also using CAR T cells to treat autoimmune diseases.[27]
What Are the Challenges in Making Car T Widely Available?
DR. JUNE: Whenever a new technology comes out, there are always some hiccups and bottlenecks. With CAR T cells, the biggest challenge is clearly the manufacturing capacity in the industry. These are the most complex medicines ever made; they’re made individually for each patient. There’s often a long waiting list for people to get therapy, even though it’s FDA approved.[28]
We’re thrilled to see long remissions that may, in fact, be a cure. At the same time, we’re also concerned about the financial cost. When you add in the cost of treating CRS and other complications, the cost can reach one million dollars per patient. We’d like to see research done now to make CAR T more efficient and increase affordability to all patients.[29]
What Inspires You? What Keeps You Going?
DR. JUNE: We’ve seen many of these Lazarus cases—where older people with leukemia or lymphoma had made their funeral arrangements, and children whose parents have given up hope because no treatment was working. The patients have been heroic to volunteer. At first, we had no idea what would happen, and now helping them is what keeps me going.[30]
Resources
For more on Emily Whitehead’s story:
- See the 2022 documentary Of Medicine and Miracles—ofmedicineandmiraclesfilm.com—which details Dr. June’s research and his creativity in treating Emily.
- Read her story from the perspective of her doctors at Children’s Hospital of Philadelphia (CHOP)—chop.edu/news/emily-whitehead-first-pediatric-patient-receive-car-t-cell-therapy-celebrates-cure-10-years.
- Learn about how Emily’s family contributes to cancer research through the Emily Whitehead Foundation—emilywhiteheadfoundation.org.
For CAR T resources:
- To learn more about CHOP’s cancer immunotherapy program—chop.edu.
- Blood & Marrow Transplant Information Network (BMT InfoNet)—bmtinfonet.org—is a leading advocacy organization for transplant and CAR T-cell therapy recipients, before, during, and after treatment. Their website includes a directory of CAR T-cell therapy centers.
- To find treatment centers near you that are authorized to administer CAR T therapy, check The ASCO Post, whichis published under the auspices of the American Society of Clinical Oncology—https://ascopost.com/issues/may-25-2018/treatment-centers-authorized-to-administer-car-t-cell-therapy/.
For more on Dr. Carl June:
- See his bio and information about his laboratory on University of Pennsylvania websites—https://www.med.upenn.edu/cci/junelab/; https://pathology.med.upenn.edu/department/people/447/carl-h-june.
https://www.pennmedicine.org/news/news-blog/2023/august/carl-june-on-the-boundless-potential-of-car-t-cell-therapy - Read about Dr. June’s life on the American Association for Cancer Research (AACR) website, “Dr. Carl H. June: Forging a Path for Cancer Cell Therapy”— https://leadingdiscoveries.aacr.org/dr-carl-h-june-forging-a-path-for-cancer-cell-therapy/.
- Watch the Cell & Gene The Podcast interview quoted in this Q&A— https://youtu.be/1pqMxYbfzIw?si=wBl5qOCgebHy3y2Q.
- Watch Dr. June’s November 2018 TED Talk— https://www.ted.com/talks/carl_june_a_living_drug_that_could_change_the_way_we_treat_cancer?utm_campaign=tedspread&utm_medium=referral&utm_source=tedcomshare.
Dr. Carl June is Director of the Center for Cellular Immunotherapies and Director of the Parker Institute for Cancer Immunotherapy in the Perelman School of Medicine at the University of Pennsylvania. A graduate of the Naval Academy in Annapolis and Baylor College of Medicine, he has published more than 350 manuscripts, and is the recipient of numerous prizes and honors, including election to the Institute of Medicine in 2012 and the American Academy of Arts and Sciences in 2014, as well as being named one of Time Magazine’s 100 Most Influential People in 2018, and receiving the Breakthrough Prize in Life Sciences 2024.
[1] Dr. Carl June in “An Interview with Dr. Carl June,” Cell & Gene The Podcast with Erin Harris, posted on YouTube 22 July, 2022 by Life Science Connect, https://youtu.be/1pqMxYbfzIw?si=3nVbLA8jNCJFIYP9.
[2] Dr. Carl June in “A ‘living drug’ that could change the way we treat cancer,” TEDMED 2018, posted November 2018, https://www.ted.com/talks/carl_june_a_living_drug_that_could_change_the_way_we_treat_cancer/transcript?language=en.
[3] TED
[4] TED
[5] Dr. Carl June, interview for Superhuman Body, MacGillivray Freeman Films (MFF), released May 2024.
[6] MFF
[7] TED
[8] TED
[9] TED
[10] Podcast
[11] MFF
[12] MFF
[13] MFF
[14] TED
[15] TED
[16] TED, Podcast
[17] MFF
[18] TED, Podcast
[19] TED
[20] MFF
[21] TED
[22] TED
[23] Podcast
[24] Podcast
[25] MFF
[26] Podcast
[27] Podcast
[28] Podcast
[29] TED
[30] Podcast