Ultrasound is not just your father’s diagnostic tool any more. More and more sophisticated ultrasound tools are being developed not only for diagnosing cancers, but also for treating them.
Dr. Robert Mattrey, M.D., could have retired from the University of California, San Diego, but the promise of being able to invent new uses for ultrasound lured him to The University of Texas Southwestern Medical Center. He came in 2015 as a professor of radiology and the Advanced Imaging Center, with the help of a Recruitment of Established Investigators Award from CPRIT. His role is to organize and lead the Translational Research in Ultrasound Theranostics (TRUST) program.
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Ultrasound is not just your father’s diagnostic tool any more. More and more sophisticated ultrasound tools are being developed not only for diagnosing cancers, but also for treating them.
Dr. Robert Mattrey, M.D., could have retired from the University of California, San Diego, but the promise of being able to invent new uses for ultrasound lured him to The University of Texas Southwestern Medical Center. He came in 2015 as a professor of radiology and the Advanced Imaging Center, with the help of a Recruitment of Established Investigators Award from CPRIT. His role is to organize and lead the Translational Research in Ultrasound Theranostics (TRUST) program.
Now this clinician scientist has developed a way to use ultrasound in combination with gene therapy to treat an otherwise deadly blood cancer in children. Mattrey’s team has received funding from the Department of Defense to conduct preliminary studies leading to a clinical trial in children.
The cancer, Acute Lymphoblastic Leukemia (ALL), can often be treated successfully with enzyme therapy. But if the cancer comes back after this initial treatment, it is deadly. A $600,000 gene-therapy immune-cell treatment called CAR-T cell therapy often works, but is expensive, time-consuming, and difficult. A patient’s white blood cells are harvested, shipped to a laboratory in Pennsylvania, genetically altered with the aid of a virus, and shipped back; meanwhile, the patient’s normal white blood cells are destroyed before the genetically altered ones are infused to replace them. Overall, the process takes 6-8 weeks, and patients may die waiting.
Dr. Mattrey plans to use microbubbles — an FDA-approved diagnostic agent for ultrasound — to get the altered genes directly into a patient’s white blood cells within minutes. The microbubbles, which are tiny encased bubbles of gas, about 1/3 the size of a red blood cell, are coated with the same gene used in the CAR-T therapy. The microbubbles, when injected into a patient’s bloodstream, seek out the desired white blood cells.
After about 10 minutes, using ultrasound, a non-invasive technique, Dr. Mattrey can place a probe on a patient’s skin over a major vein. As the blood passes under the ultrasound probe, the microbubbles squeeze and inject the genetic material directly into the white blood cells, eliminating the need to use viruses to penetrate the cell.
The new genes help activate the patient’s own immune system to fight and destroy the cancer cells. The microbubbles themselves harmlessly break down and are exhaled from the body within 15-20 minutes. “We have shown that we can target the cells and express the gene,” Dr. Mattrey says, and he has shown in preliminary studies that he can deliver genes to circulating cells. He acknowledges there are challenges remaining: “We hope that we can transfect enough immune cells, and the delivered genes will express enough proteins to last long enough, that they will be able to kill all the cancer cells.”
Dr. Mattrey’s research team is also developing nanoparticles that can be used to improve enzyme therapy for ALL by preventing a devastating immune response. Dr. Mattrey received his undergraduate and master’s degrees in electrical engineering, as well as his M.D., from the State University of New York at Buffalo. He was professor of radiology at UCSD for more than 30 years, and has been continuously funded by research grants for nearly 40 years. He directed UCSD’s Molecular Imaging Program and the Radiology Clinician/Scientist Program, and co-directed the Institute of Engineering in Medicine. He has also been a consultant for the FDA Center for Drug Evaluation & Research.
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