Switchable CAR T cell strategy against osteosarcoma.

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor T (CAR T) cell therapy is effective for blood cancers but faces challenges in treating solid tumors like pediatric sarcomas.
• Osteosarcoma (OS) remains a difficult-to-treat solid tumor, necessitating novel therapeutic approaches.

Purpose of the Study:

• To develop and evaluate a switchable CAR T cell strategy for targeting osteosarcoma (OS).
• To investigate the potential of targeting B7-H3, an immune checkpoint inhibitor, in OS.
• To assess the efficacy of an anti-B7-H3 antibody as a switch molecule to control anti-FITC CAR T cell activity.

Main Methods:

• Analyzed B7-H3 expression in OS cell lines.
• Developed anti-FITC CAR T cells and an anti-B7-H3-FITC monoclonal antibody (mAb) switch molecule.
• Evaluated in vitro effector functions (cytotoxicity, cytokine production) and cell migration.
• Assessed in vivo antitumor activity in an OS NSG mouse model.

Main Results:

• Anti-FITC CAR T cell effector functions against OS were dependent on the anti-B7-H3-FITC mAb switch.
• OS cells promoted migration of anti-FITC CAR T cells.
• In vivo, the anti-B7-H3 mAb localized to the tumor and bound OS cells.
• Anti-FITC CAR T cells exerted antitumor effects in mice only when the switch molecule was present.

Conclusions:

• Switchable CAR T cell platforms, utilizing an anti-B7-H3-FITC mAb, can redirect cytotoxic activity against osteosarcoma.
• This strategy demonstrates potential as a viable therapeutic approach for OS treatment.