ith the usual mix of anticipation and apprehension, Kaitlyn Johnson is getting ready to go to her first summer camp. She’s looking forward to meeting new friends and being able to ride horses, swim and host tea parties. She’s also a little nervous and a little scared, like any 7-year-old facing her first sleepaway camp.
But the wonder is that Kaitlyn is leaving the house for anything but a medical facility. Diagnosed with leukemia when she was 18 months old, her life has been consumed with cancer treatments, doctors’ visits and hospital stays.
Acute lymphoblastic leukemia is the most common cancer among young children, accounting for a quarter of all cancer cases in kids, and it has no cure. For about 85% to 90% of children, the leukemia can, however, be effectively treated through chem
If it is not eliminated and comes back, it is, more often than not, fatal. Rounds of chemotherapy can buy patients time, but as the disease progresses, the periods of remission get shorter and shorter. “The options for these patients are not very good at all,” says Dr. Theodore Laetsch, a pediatrician at the University of Texas Southwestern Medical Center.
When Kaitlyn’s cancer wasn’t controlled after three years and round after round of chemotherapy drugs, her doctors had little else to offer. “They said, ‘This did nothing, it didn’t touch it,'” says Kaitlyn’s mother Mandy, a dental assistant from Royce City, Texas. “My stomach just dropped.” Kaitlyn could receive a bone-marrow transplant, but only about half of those procedures are successful, and there was a good chance that she would reject the donor cells. If that happened, her chances of surviving were very small.
In a calculated gamble, her doctors suggested a radical new option: becoming a test subject in a trial of an experimental therapy that would, for the first time, use gene therapy to train a patient’s immune system to recognize and destroy their cancer in the same way it dispatches bacteria and viruses. The strategy is the latest development in immunotherapy, a revolutionary approach to cancer treatment that uses a series of precision strikes to disintegrate cancer from within the body itself. Joining the trial was risky, since other attempts to activate the immune system hadn’t really worked in the past. Mandy, her husband James and Kaitlyn traveled from their home in Texas to Children’s Hospital of Philadelphia (CHOP), where they stayed in a hotel for eight weeks while Kaitlyn received the therapy and recovered. “The thought crossed my mind that Kaitlyn might not come home again,” says Mandy. “I couldn’t tell you how many times I would be in the bathroom at the hospital, spending an hour in the shower just crying, thinking, What are we going to do if this doesn’t help her?”
But it did. After receiving the therapy in 2015, the cancer cells in Kaitlyn’s body melted away. Test after test, including one that picks up one cancer cell in a million, still can’t detect any malignant cells lurking in Kaitlyn’s blood. What saved Kaitlyn was an infusion of her own immune cells that were genetically modified to destroy her leukemia. “You take someone who essentially has no possibility for a cure–almost every single one of these patients dies–and with [this] therapy, 90% go into remission,” says Dr. David Porter, director of blood and bone-marrow transplantation at the University of Pennsylvania. Such radical immune-based approaches were launched in 2011 with the success of intravenous drugs that loosen the brakes on the immune system so it can see cancer cells and destroy them with the same vigor with which they attack bacteria and viruses. Now, with the genetically engineered immune cells known as chimeric antigen receptor (CAR) T cells that were used in Kaitlyn’s study, doctors are crippling cancer in more precise and targeted ways than surgery, chemotherapy and radiation ever could. While the first cancer immunotherapies were broadly aimed at any cancer, experts are now repurposing the immune system into a personalized precision treatment that can not only recognize but also eliminate the cancer cells unique to each individual patient.
What makes immune-based therapies like CAR T cell therapy so promising–and so powerful–is that they are a living drug churned out by the patients themselves. The treatment isn’t a pill or a liquid that has to be taken regularly, but a one-hit wonder that, when given a single time, trains the body to keep on treating, ideally for a lifetime.
“This therapy is utterly transformative for this kind of leukemia and also lymphoma,” says Stephan Grupp, director of the cancer immunotherapy program at CHOP and one of the lead doctors treating patients in the study in which Kaitlyn participated.
Eager to bring this groundbreaking option to more patients, including those with other types of cancers, an advisory panel for the Food and Drug Administration voted unanimously in July to move the therapy beyond the testing phase, during which several hundred people have been able to take advantage of it, to become a standard therapy for children with certain leukemias if all other treatments have failed. While the FDA isn’t obligated to follow the panel’s advice, it often does, and it is expected to announce its decision in a matter of weeks.
Across the country, doctors are racing to enroll people with other cancers–breast, prostate, pancreatic, ovarian, sarcoma and brain, including the kind diagnosed in Senator John McCain–in hundreds of trials to see if they, too, will benefit from this novel approach. They are even cautiously allowing themselves to entertain the idea that this living drug may even lead to a cure for some of these patients. Curing cancers, rather than treating them, would result in a significant drop in the more than $120 billion currently spent each year on cancer care in the U.S., as well as untold suffering.
This revolutionary therapy, however, almost didn’t happen. While the idea of using the body’s immune cells against cancer has been around for a long time, the practical reality had proved daunting. Unlike infection-causing bacteria and viruses that are distinctly foreign to the body, cancer cells start out as healthy cells that mutate and grow out of control, and the immune system is loath to target its own cells.
“Only a handful of people were doing the research,” says Dr. Carl June, director of the Center for Cellular Immunotherapy at the University of Pennsylvania’s Abramson Cancer Center and the scientist who pioneered the therapy. A graduate of the U.S. Naval Academy, June is all too familiar with the devastating effects of cancer, having lost his first wife to ovarian cancer and battled skin cancer himself. Trial after trial failed as reinfusions of immune cells turned out to be more of a hit-or-miss endeavor than a reliable road to remission.
After spending nearly three decades on the problem, June zeroed in on a malignant fingerprint that could be exploited to stack the deck of a cancer patient’s immune system with the right destructive cells to destroy the cancer.
In the case of leukemias, that marker turned out to be CD19, a protein that all cancerous blood cells sprout on their surface. June repurposed immune cells to carry a protein that would stick to CD19, along with another marker that would activate the immune cells to start attacking the cancer more aggressively once they found their malignant marks. Using a design initially developed by researchers at St. Jude Children’s Research Hospital for such a combination, June and his colleague Bruce Levine perfected a way to genetically modify and grow these cancer-fighting cells in abundance in the lab and to test them in animals with leukemia. The resulting immune platoon of CAR T cells is uniquely equipped to ferret out and destroy cancer cells. But getting them into patients is a complex process. Doctors first remove a patient’s immune cells from the blood, genetically tweak them in the lab to carry June’s cancer-targeting combination and then infuse the modified cells back into the patient using an IV.
Because these repurposed immune cells continue to survive and divide, the therapy continues to work for months, years and, doctors hope, perhaps a lifetime. Similar to the way vaccines prompt the body to produce immune cells that can provide lifelong protection against viruses and bacteria, CAR T cell therapy could be a way to immunize against cancer. “The word vaccination would not be inappropriate,” says Dr. Otis Brawley, chief medical officer of the American Cancer Society