Abstract: Chimeric antigen receptors (CARs) are provided. When the CARs herein are expressed on the surface of immune cells, such immune cells may be directed to osteosarcoma cells. In a murine intraperitoneal model, the tumor growth was significantly delayed for T cells expressing a CAR comprising a scFv from TP1 or TP3 antibodies. Immune cells expressing the CARs herein display therapeutic effect in the form of decreased tumor volume in a murine model simulating metastatic osteosarcoma. Combined with the finding that stem cells from healthy bone marrow were not significantly affected by T cells expressing any of the CARs, the CARs may be used for the treatment of osteosarcoma.

Abstract: Provided herein are proteins comprising a novel antigen binding domain. Said antigen binding domain, and proteins comprising it, are able to bind to osteosarcoma cells under physiological conditions. The antigen binding domain comprises an antibody light chain variable domain (VL) and an antibody heavy chain variable domain (VH), each comprising three complementarity determining regions (CDRs) flanked by human framework sequences. The human framework sequences reduces the risk of triggering unwanted immunogenic responses against the antigen binding domain. This may be especially important in a therapeutic setting wherein a drug is administered repeatedly to a human osteosarcoma patient.

Abstract: Novel chimeric antigen receptors (CARs) are provided. When the CARs herein are expressed on the surface of immune cells, such immune cells may be directed to osteosarcoma cells as demonstrated with our in vivo data. In a murine intraperitoneal model, the tumor growth was significantly delayed for T cells expressing a CAR comprising a scFv from TP1 or TP3 antibodies. Immune cells expressing the CARs herein display therapeutic effect in the form of decreased tumor volume in a murine model simulating metastatic osteosarcoma. Combined with the finding that stem cells from healthy bone marrow were not significantly affected by T cells expressing any of the CARs, this disclosure provides an attractive cell therapeutic alternative for treatment of osteosarcoma.