Physician-scientist Theodore Scott Nowicki, MD, PhD, an assistant professor in the department of pediatrics hematology/oncology and microbiology, immunology, & molecular genetics at the David Geffen School of Medicine at UCLA, has been awarded the Hero Grant from MIB Agents, a nonprofit organization dedicated to improving outcomes for children and young adults with osteosarcoma.
The award, which comes with $100,000, the highest funding level awarded through the OutSmarting Osteosarcoma program, will support Nowicki's research into the development of a next-generation CAR-T cell therapy for osteosarcoma, the most common bone cancer in children and adolescents.
CAR-T cell therapy is a form of immunotherapy that uses a patient's own immune cells to fight cancer. The treatment works by collecting and genetically engineering T cells to recognize and attack cancer cells. While CAR-T therapies have shown remarkable success in certain blood cancers, they have been less effective against solid tumors such as osteosarcoma, where the tumor's surrounding environment can suppress immune activity and limit the treatment's ability to eliminate cancer cells.
Nowicki's research aims to overcome this challenge through a novel "armed" CAR T platform that targets GD2, a protein commonly found on osteosarcoma cells. In addition to recognizing and attacking tumor cells, the engineered CAR-T cells are designed to release increased amounts of tumor necrosis factor-alpha, or TNF-alpha, an immune-signaling molecule that helps strengthen the anti-tumor response and resist immune suppression within the tumor microenvironment. Importantly, the TNF-alpha is only secreted in the presence of the tumor cells, which increases the safety profile of the product.
The grant will support expanded preclinical studies evaluating the safety and effectiveness of the TNF-alpha-armed GD2 CAR-T cells in laboratory and animal models of osteosarcoma for future clinical trials. Researchers will compare the engineered therapy to conventional GD2 CAR-T cells and investigate how TNF-alpha enhances anti-tumor activity within the tumor microenvironment. The team will also use advanced molecular profiling technologies to better understand how the treatment influences interactions between cancer cells and the immune system.
"Patients with relapsed or metastatic osteosarcoma continue to face poor outcomes with limited treatment options," said Nowicki, who is also a member of the UCLA Health Jonsson Comprehensive Cancer Center and the UCLA Broad Stem Cell Research Center. "This funding will help us advance a promising new immunotherapy strategy that has the potential to improve outcomes while reducing reliance on toxic treatments such as chemotherapy and radiation."
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