Crystal Mackall, MD, receives her second research grant from foundation.
STAMFORD, Conn., July 2, 2024 — A $500,000 grant from Alliance for Cancer Gene Therapy (ACGT) will support Stanford University scientists who are developing a CAR T-cell therapy with remote-control technology to treat people with solid tumors.
The grant was awarded to Crystal Mackall, MD, who is the founding director of the Stanford Center for Cancer Cell Therapy, the director of the Parker Institute for Cancer Immunotherapy at Stanford University, the Ernest and Amelia Gallo Family Professor of Pediatrics and Internal Medicine at Stanford University, the associate director of the Stanford Cancer Institute and leader of the Stanford University Cancer Immunology and Immunotherapy Program. Dr. Mackall is also an ACGT Research Fellow and a member of the ACGT Scientific Advisory Council.
Dr. Mackall is a trailblazer in advancing CAR T-cell therapy, which is a type of cell and gene therapy that modifies a patient’s T cells to more effectively find cancer cells. She received a research grant from ACGT in 2016 to develop a CAR T-cell therapy targeting the protein GD2 in children with osteosarcoma (bone cancer) and neuroblastoma (nerve cell cancer). This research led to a clinical trial for the two types of cancer and translated to a clinical trial for children with a devastating brain tumor called diffuse midline glioma.
The newest grant from ACGT will support Dr. Mackall’s development of a remote-control CAR T-cell therapy called “SNIP-CAR” that targets cancer cells expressing the protein B7H3. This protein is expressed in several solid tumors, including ovarian and lung cancer.
The remote-control feature allows scientists to turn the engineered cells “on” and “off” as needed to reduce toxicities and help regain energy. SNIP-CARs contain a molecule (called a protease) that continuously “snips” the CAR molecule in half, preventing its function, unless a drug is present to inhibit the protease. SNIP-CARs are “off” at baseline but are activatable in the presence of the drug.
“In mouse models where standard CAR T cells killed the animals due to toxicity, stopping the drug (turning the cells off) after the animals became ill allowed complete recovery,” Dr. Mackall says. “Surprisingly, in settings where toxicity was not an issue, SNIP-CARs plus daily dosing of the drug resulted in greater tumor control than seen with standard CAR T cells. This is due to the variations in drug levels by drug metabolism, which provided the CAR T cells with periods of activation followed by periods of ‘rest.’”
Funding from ACGT will help generate the necessary processes, procedures and materials needed to test SNIP-CARs in a clinical trial for patients with B7H3-expressing solid cancers.
“The proposal will amplify ACGT investment by leveraging substantial infrastructure in place at Stanford to greatly accelerate clinical testing of a cutting-edge cancer gene therapy platform for patients with critical unmet need,” Dr. Mackall says.
“Dr. Mackall is an esteemed cancer scientist and has already used funding from ACGT to advance a CAR T-cell therapy for children with aggressive forms of osteosarcoma, neuroblastoma and diffuse midline glioma,” says Kevin Honeycutt, ACGT chief executive officer and president. “This latest proposal looks to address some of the challenges of using cell and gene therapy for solid tumors, such as T-cell exhaustion and patient toxicities. We are excited to support Dr. Mackall’s ‘SNIP-CAR’ therapy and are optimistic in its efficacy as the next evolution in developing a curative CAR T-cell therapy for cancer.”
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Alliance for Cancer Gene Therapy (ACGT)
For more than 20 years, Alliance for Cancer Gene Therapy (ACGT) has funded scientific research to bring innovative treatment options using cancer cell and gene therapy to people living with deadly cancers. These treatments continue to save the lives of many blood cancer patients and offer new hope to all people diagnosed with cancer. ACGT is currently focused on funding talented visionaries whose scientific advancements are driving the development of groundbreaking treatments for glioblastoma, melanoma, sarcoma, ovarian, lung, prostate, and pancreatic cancers.
100% of all public donations raised by Alliance for Cancer Gene Therapy directly support research and programs. For more information, visit acgtfoundation.org, call (203) 358-5055, or join the Alliance for Cancer Gene Therapy community on Facebook, Twitter, LinkedIn, Instagram and YouTube.
