Hidalgo, LauraSomovilla-Crespo, BeatrizGarcía-Rodriguez, PatriciaMorales-Molina, AlvaroRodriguez-Milla, Miguel AGarcia-Castro, Javier2023-05-122023-05-122023-04-16Cancer Immunol Immunother. 2023 Aug;72(8):2623-2633.http://hdl.handle.net/20.500.12105/16059Immunotherapy with chimeric antigen receptor T (CAR T) cells has changed the treatment of hematological malignances, but they are still a challenge for solid tumors, including pediatric sarcomas. Here, we report a switchable CAR T cell strategy based on anti-FITC CAR T cells and a switch molecule conjugated with FITC for targeting osteosarcoma (OS) tumors. As a potential target, we analyzed the expression of B7-H3, an immune checkpoint inhibitor, in OS cell lines. In addition, we evaluate the capacity of an anti-B7-H3 monoclonal antibody conjugated with FITC (anti-B7-H3-FITC mAb) to control the antitumor activity of anti-FITC CAR T cells. The effector functions of anti-FITC CAR T cells against OS, measured in vitro by tumor cell killing activity and cytokine production, are dependent on the presence of the anti-B7-H3-FITC mAb switch. Moreover, OS cells stimulate anti-FITC CAR T cells migration. In vivo, anti-B7-H3 mAb penetrates in the tumor and binds 143B OS tumor cells. Furthermore, anti-FITC CAR T cells reach tumor region and exert antitumor effect in an OS NSG mouse model only in the presence of the switch molecule. We demonstrate that anti-B7-H3-FITC mAb redirects the cytotoxic activity of anti-FITC CAR T cells against OS tumors suggesting that switchable CAR T cell platforms might be a plausible strategy against OS.engVoRhttp://creativecommons.org/licenses/by/4.0/B7-H3CAR TImmunotherapyOsteosarcomaAtribución 4.0 Internacional370620347282623-263310.1007/s00262-023-03437-z1432-0851Cancer immunology, immunotherapy : CIIopen access