Solid tumors contribute disproportionately to the morbidity and mortality of all pediatric patients with cancer despite aggressive management with multimodality therapy. This problem is especially acute in children and young adults with relapsed or refractory solid tumors. Survival rates have remained relatively unchanged for decades, so new therapeutic strategies such as chimeric antigen receptor (CAR) T cells seem promising to enhance survival without overlapping toxicities with conventional chemotherapy.
B7-H3-specific chimeric antigen receptor (CAR) T-cell therapy has potential because B7-H3 is expressed at high levels on multiple solid tumor types, with limited expression on normal tissues. However, most B7-H3-CARs explored thus far have been 2nd generation (2G) CARs. Since 2G-CAR T cells targeting other solid tumor antigens have limited antitumor activity in clinical studies, there is significant concern that 2G-CAR T cells targeting B7-H3 will have limited benefit as well.
Researchers at St. Jude looked at both CD28 and 41BB co-stimulation and compared the effector functions with 2G CARs. One of the two designed CD28.ζ CARs emerged as the lead CAR, and from there they developed a B7-H3-specific chimeric antigen receptor construct including a costimulatory domain consisting of 41BB ligand expressed on the immune cell surface. The technology combining B7-H3-CAR with surface 41BB ligand expression enhances B7-H3-CAR effector function against B7-H3-positive malignant cells.
Solid tumor, chimeric antigen receptor (CAR) T cells, Biologic, B7-H3-specific, CD28 and 41BB co-stimulation, CD276, neuroblastoma, osteosarcoma, rhabdomyosarcoma, and prostate, ovarian, colorectal, lung cancer.
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