Unleashing the hounds.
Crystal Mackall, MD
Stanford University
“To use a patient’s own immune system to fight cancer, we need to turn that patient’s CAR T cells into bloodhounds. We train them to sniff out and kill cancer cells,” says Crystal Mackall, MD, of Stanford University (Stanford, Calif.). “T cells find tumors by being trained (genetically engineered) to find specific biomarkers, and different cancers express different biomarkers.”
When Dr. Mackall was awarded a grant from Alliance for Cancer Gene Therapy, “it was already established that with genetic engineering, CAR T cells could be successfully trained to find and destroy cancers that express the protein biomarker CD19, which is expressed by leukemia and lymphoma, for example,” says Dr. Mackall, a member of the National Academy of Medicine. “We also knew that pediatric neuroblastoma and osteosarcoma express a different biomarker, a fatty sugar known as GD2.”
With different genetic engineering, Dr. Mackall developed a new iteration of CAR T-cell therapy, successfully training T cells to find and kill solid tumors that express GD2 in much the same way T cells are trained to find and kill cancers that express CD19.
The Alliance-funded portion of Dr. Mackall’s research was complex and mission-critical to advancing the GD2 strategy out of the laboratory and into clinical trials. In the process, Dr. Mackall discovered that GD2 also is expressed by a devastating pediatric brain tumor known as diffuse intrinsic pontine glioma (DIPG). This breakthrough greatly increases the value promise of this potential new CAR T-cell therapy.
Dr. Mackall hopes to unleash her new T cell bloodhounds to sniff out GD2 in diffuse intrinsic pontine glioma at Stanford and in neuroblastoma and osteosarcoma in 10 centers across the United States.
In addition to effectively eliminating cancers, an advantage of CAR T-cell and other gene therapies is that they don’t take such a tremendous toll on a patient’s general health and well-being. Says Dr. Mackall, “anybody who’s experienced or witnessed cancer knows that for the last 40 years, existing treatments really beat down a patient’s body in general and immune system in particular – and all too often without good results. Today we have very advanced new technologies and solid evidence that the immune system can be used as a powerful weapon, yet we’re treating many cancers like it’s still the 1980s.”
Update: Following Dr. Mackall’s first grant from ACGT, she received a second grant to develop a SNIP CAR T-cell therapy for solid tumors. The SNIP technology allows for remote control of the CAR T cells to increase potency and safety for patients with solid tumors.
This Alliance for Cancer Gene Therapy Research Fellow is funded in part by Swim Across America and Wendy Walk.
“Alliance for Cancer Gene Therapy is a very forward-thinking organization. It recognized the potential for new cancer gene therapies very early on and that foresight is paying off. In the next 50 years, I think we’re going to see cell and gene therapy become the part of medicine where the most dramatic advances are made.”
