CAR T-cells targeting FGFR4 and CD276 simultaneously show potent antitumor effect against childhood rhabdomyosarcoma

• Published in: Nature communications Vol. 15; no. 1; pp. 6222 - 17
• Main Authors: Tian, Meijie, Wei, Jun S., Cheuk, Adam Tai-Chi, Milewski, David, Zhang, Zhongmei, Kim, Yong Yean, Chou, Hsien-Chao, Liu, Can, Badr, Sherif, Pope, Eleanor G., Rahmy, Abdelrahman, Wu, Jerry T., Kelly, Michael C., Wen, Xinyu, Khan, Javed
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 38/5; 49/91; 631/250/2152/1566/1618; 631/250/2520; 631/67/1059/2325; 631/67/2332; 82/51; 82/81; Animals; Anticancer properties; Antigens; Antitumor activity; Antitumor agents; B7 Antigens - genetics; B7 Antigens - immunology; B7 Antigens - metabolism; CD28 antigen; CD8 antigen; Cell activation; Cell culture; Cell Line, Tumor; Cell therapy; Child; Childhood; Children; Chimeric antigen receptors; Female; Fibroblast growth factor receptor 4; Growth factors; Heterogeneity; Humanities and Social Sciences; Humans; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred NOD; Mice, SCID; Microenvironments; multidisciplinary; MyoD Protein - genetics; MyoD Protein - metabolism; Receptor, Fibroblast Growth Factor, Type 4 - genetics; Receptor, Fibroblast Growth Factor, Type 4 - metabolism; Receptors; Receptors, Chimeric Antigen - immunology; Receptors, Chimeric Antigen - metabolism; Rhabdomyosarcoma; Rhabdomyosarcoma - genetics; Rhabdomyosarcoma - immunology; Rhabdomyosarcoma - therapy; Science; Science (multidisciplinary); Solid tumors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Target recognition; Transmembrane domains; Tumors; Tyrosine; Xenograft Model Antitumor Assays; Xenotransplantation

Chimeric antigen receptor (CAR) T-cells targeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in rhabdomyosarcoma (RMS), are already in the clinical phase of development, but tumour heterogeneity and suboptimal activation might hamper their potency. Here...