B7-H3 targeted CAR-T cells show highly efficient anti-tumor function against osteosarcoma both in vitro and in vitro

Abstract Background Osteosarcoma(OS)is one of the foremost common dangerous bone tumors, which mainly happens in children and youths. The combination of surgery, radiotherapy and chemotherapy are the common therapies for osteosarcoma treatment. Unfortunately, many patients still experience recurrence or lung metastasis after the current treatments against osteosarcoma. Thus, developing new therapies is urgently needed for improving the current osteosarcoma treatment effect. CAR-T, a cellular immunotherapy with genetically engineered T cells bearing chimeric antigen receptor targeting specific tumor-associated antigen, has been proved to be an effective therapy against acute lymphoblastic leukemia Thus, CAR-T is a potentially effective therapy for osteosarcoma treatment. Methods A CAR gene targeting B7-H3 antigen was constructed into lentiviral vector through molecular biology techniques. Then, the CAR gene is transferred to T cells through lentiviral delivery system and the CAR-T cells were largely expanded using in vitro culture technology. The in vitro anti-tumor effect of CAR-T cells was evaluated through Real Time Cell Analysis system (RTCA) and ELISA assay. The in vivo anti-tumor capabilities of CAR-T cells were evaluated using the patient-derived xenografts (PDX) model of osteosarcoma. Results The third-generation CAR-T cells we constructed could target the B7-H3 antigen, and the T cell phenotype was also consistent with normal T cells; In vitro levels had a clear antitumor effect; The in vivo level embodied the superior antitumor effect in the osteosarcoma PDX model. Conclusion Our study showed that B7-H3 targeted CAR-T cells had high anti-tumor efficacy against osteosarcoma both in vitro and in vivo, which proved that B7-H3 targeted CAR-T is an potentially effective treatment for osteosarcoma.