CAR T-Cell for Brain Tumors
Chimeric antigen receptor T-cell therapy weaponizes our natural immune cells to make them more effective cancer killers. It extracts a small number of white blood cells, called T cells, from a patient’s blood, then genetically modifies them to kill cancer. Those cells are then infused back into the patient, where they replicate into a vast army of cancer killers. The entire process takes about two weeks, as opposed to other processes that can take months.
CAR T-cell immunotherapy has had significant success in battling blood cancers, but it has been less effective against solid tumors. Lee’s new finding could enhance its ability to target these tumors that now resist CAR T-cell treatment.
His new work identifies specific targets on glioblastoma and DIPG cells that the immunotherapy could exploit. When tested in mice, the approach was very effective – the tumors shrank or disappeared, and the weaponized immune cells proved long-lasting. The approach also avoided side effects that have previously hampered its use in people.
Particularly notable was the approach’s effectiveness against DIPG, a cancer that threads itself through the brain, making it extremely hard to treat. Lee’s immunotherapy approach shrank the tumors and improved survival among lab mice. The scientists note that the cancer’s invasive nature likely will continue to pose a challenge, especially when the cancer’s tentacles extend into vital areas of the brain, but the researchers were encouraged by the promising results.
Many solid tumors share the same vulnerabilities Lee’s team identified in glioblastoma and DIPG. That suggests the results could have wider applications for solid tumors.
“We have already begun to see if we can use this same therapy to treat other tumors, like melanoma, breast cancer and the pediatric muscle tumor rhabdomyosarcoma, in the lab,” said Lee, a pediatric oncologist at UVA Children’s and UVA Cancer Center. “My team in the lab is working incredibly hard to understand how we can bring new and safer CAR T-cell therapies to the citizens of Virginia and beyond. Our findings in brain tumors represent a huge leap forward in doing just that, but there is much more work to be done.”
While the new discovery has shown exciting promise, significantly more research will be needed before it can be translated into better treatments for patients. This type of cutting-edge research is an urgent mission of UVA Cancer Center, which is one of only 52 cancer centers in the country to be designated as a Comprehensive Cancer Center by the National Cancer Institute. The designation recognizes elite cancer centers with the most outstanding cancer research and treatment programs in the nation.
UVA Cancer Center is the only Comprehensive Cancer Center in Virginia.
Reference: Cobb DA, Rossi J de, Liu L, An E, Lee DW. Targeting of the alphav beta3 integrin complex by CAR-T cells leads to rapid regression of diffuse intrinsic pontine glioma and glioblastoma. J Immunother Cancer. 2022;10(2):e003816. doi: 10.1136/jitc-2021-003816
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