Top Stanford researcher is harnessing patients’ own immune systems to treat cancer
Over the past 50 years, researchers have made incredible progress in treating pediatric cancer. While about 60% of young cancer patients died from their disease in the mid-1970s, today, 85% of patients survive. This progress is only possible through clinical trials led by academic medical centers like Lucile Packard Children’s Hospital Stanford.
Despite these advances, cancer remains the leading cause of death by disease among children aged 15 and under. For those who can be cured, harsh treatments often trigger health challenges later in life, such as organ damage, infertility, or secondary cancers.
Illustration by Alece Birnbach
Crystal Mackall, MD, the Ernest and Amelia Gallo Family Professor, professor of pediatrics and medicine, and center director for the Parker Institute for Cancer Immunotherapy at Stanford Medicine, is leading the charge to offer hope for kids who need it most. For more than 40 years, Mackall has been a pioneer in cancer immunotherapy—a field that harnesses the body’s own immune cells to fight disease. In 2017, Mackall launched the Center for Cancer Cell Therapy at Stanford to propel breakthroughs from the lab to patients’ bedsides as quickly as possible.
“Stanford is, in my opinion, the place where the most creative science is done in all the world,” Mackall says. “I wanted to develop cell therapies here because I knew I would be able to work with some of the most amazing minds—investigators who are interested in things like synthetic biology, artificial intelligence, translational research, and human immunology.”
Mackall’s team is leading revolutionary improvements to chimeric antigen receptor (CAR) T-cell therapies. This approach, which has been remarkably effective against some blood cancers, engineers a patient’s immune system to seek and destroy cancer cells. Now Mackall is working to make this treatment effective for solid cancers and brain tumors, with a major focus on children. Mackall collaborated with Michelle Monje, MD, PhD, the Milan Gambhir Professor of Pediatric Neuro-Oncology, on a major breakthrough using CAR T cells to treat diffuse intrinsic pontine glioma, a pediatric brain tumor that has been considered universally fatal—until now.
This breakthrough was catalyzed by expansive donor support, and Mackall knows it is only the beginning. She is developing what she calls “next-gen” immunotherapies—building on current technologies to make immunotherapies safer, more effective, and more cost effective.
One of these innovations is designed to improve the longevity, safety, and effectiveness of CAR T-cell therapies. Mackall and her team discovered that they could use an existing drug—an FDA-approved hepatitis pill—to “switch on” dormant CARs after they are infused back into the patientʼs body. This new method, dubbed “SNIP CAR T,” gives them an unprecedented amount of control over not only when and where the treatment is deployed, but also the level of activation.
“We’ve created a ‘remote-controlled’ CAR T-cell therapy that is tunable for each patient,” Mackall explains. “The modified CAR T cells are not only safer, but they are also more potent and more versatile than the original CAR T cells.”
Cutting-edge science like Mackall’s will require robust support from forward-thinking investors. However, this type of support can be difficult to obtain through traditional funding sources.
“Venture capital and biopharmaceutical companies don’t usually invest in rare diseases, and all children’s cancers are rare diseases,” she explains. “But our goal is to do disruptive science. We want to change the way that patients are treated in the future.”
Philanthropic support has catalyzed Mackall’s discoveries and will be critical as she forges ahead. Donors like Chris Gallo—whose family established an endowed professorship for Mackall—are committed to fueling her important work. Gallo knows that progress will happen even faster if other philanthropists join in.
“Our family has been longtime supporters of cutting-edge science like Dr. Mackall’s—research that leads to better treatments for kids,” Gallo says. “We are proud to continue this legacy with our philanthropy.”
With trailblazing success and endless possibility, Mackall is charting the course for a new era of medicine and a healthier future for children.
