Dr. Michael Jensen of Seattle Children’s Hospital is one of the leading authorities on CAR T-cell therapy. He has been working on CAR T-cell therapy for many years, and his work is proving to be very beneficial for pediatric cancer patients. This type of therapy provides hope that someday children can receive far less-toxic medicines that lead to a cure.
Dr. Jensen started his career in the late 1990s at City of Hope National Medical Center in Los Angeles, where his research looked at the technology to take immune cells from a cancer patient and genetically modify them to recognize and attack cancer cells. This is something the patient’s natural immune system can’t do. His research was groundbreaking at that time, and his lab had to build everything from scratch.
“This was similar to creating the Apollo rocket and trying to land on the moon,” Dr. Jensen said. “We had to invent and create every step of the process and make sure the quality was sufficient. Once the first cells were infused, it was literally like landing on the moon and hoping that everything went right.”
It took over a decade of small trials to work out each and every kink, and obtaining funding for something so revolutionary was challenging. One source of consistent funding came from Lauren’s Run. From the beginning, Lauren’s parents were looking for groundbreaking research that would help children with cancer. After learning of Dr. Jensen’s research, they decided that it was exactly what they were looking for and made sure proceeds from the race supported his work.
His breakthrough came in 2014, when doctors using the patient’s own immune system through CAR T-cell therapy started seeing dramatic remissions in children with leukemia who were otherwise out of options.
“Without a functioning immune system, cancer would be much more common,” explained Dr. Jensen. “Think of cancer cells as a semi-truck on a freeway down a mountainside with the brakes broken, and the gas pedal stuck on full. On the way down, the cells acquire genetic programs and mutations and become uncontrolled. The human immune system is challenged because this isn’t a virus that came from outside the body. It doesn’t help that the cancer cells create deflector screens to fool the immune system into peaceful coexistence when we would like for the immune system to attack.”
CAR T-cell therapy takes the T-cells out of the body and supercharges them. The supercharged cells are then put back into the body as a surprise attack on the cancer cells, and the deflectors are not always effective in turning off the immune response. Ideally, within a week or two, the patient goes into remission. The cells then continue to move to all parts of the body, hunting and eliminating any remaining cancer cells. Over 90% of leukemia patients whose initial treatment didn’t work go into remission when given CAR T-cell therapy!
Leukemia was the first target, but the goal is to get CAR T-cell therapy to work against other childhood cancers. CAR T-cell therapy represents a major step toward a safer cure for children. It started as an idea in the mind of brilliant researchers years ago and is now a frontline treatment for many children. But it didn’t happen overnight. It was a long process, and Lauren’s Run was with them every step of the way.
Marc and his wife, Andrea, would soon learn that DIPG is a rare brain cancer for which there is no known cure. As if that wasn’t bad enough, Raegan had the worst possible genetic mutation and was given a prognosis of 6-9 months. Both Marc and Andrea work in the medical field and began scouring the internet for information and potential clinical trials.
Just after her third birthday, Madeline had terrible leg pain and refused to walk, so Bethany took her back to the hospital. Madeline’s blood work showed that inflammation markers were very high, so doctors ordered a total body scan. They found a football-sized mass in her abdomen that had smashed her bladder and pushed into her intestines, kidney, and liver. A biopsy of the mass confirmed a diagnosis of neuroblastoma.
Another part of the APMP is the genetic predisposition program, which provides care for children who are at risk for developing cancer due to a cancer predisposition syndrome or a family history of cancer. Madeline’s younger sister, Sedona, has a known genetic disorder called hemihypertrophy. So she was referred to the genetic predisposition clinic to see if her genetic mutation was the same as Madeline’s. If a genetic link between the two was revealed, it might indicate that Sedona had a high risk of developing cancer in the future.
The PT actually helped for a time, but the pain came back. In February 2017, an MRI revealed new lesions. Once again, neuroblastoma had invaded Lauren’s body. The cancer had spread to her bones, bone marrow, lung and pelvis. In all, the imaging indicated 28 spots that were likely active tumors.
When treatment options have been exhausted, there is little hope of survival. But through CURE’s funding of the Aflac Precision Medicine Program, doctors have a new tool in their toolkit. Lauren was enrolled in the program to see if there was a genetic reason her cancer was resisting treatment. Genetic testing revealed Lauren’s tumor had a genetic mutation for which there is a drug known to be effective. Lauren was immediately enrolled in a clinical trial for lorlatinib. She was given a single pill once a day, and after only four cycles, all bone metastases and bone marrow involvement had disappeared. Incredibly, the only tumor remaining at that time showed inactive.
