B7-H3 Specific CAR T Cells for the Naturally Occurring, Spontaneous Canine Sarcoma Model

Area of Science:

• Immunology
• Oncology
• Veterinary Medicine
• Biotechnology

Background:

• Clinically relevant animal models are crucial for advancing human solid tumor immunotherapy research.
• Existing models often lack the necessary translational relevance for effective CAR T-cell therapy development.

Purpose of the Study:

• To establish a chimeric antigen receptor (CAR) T-cell treatment model using naturally occurring canine sarcomas.
• To evaluate the efficacy and safety of canine CAR T-cells targeting B7-H3 as a model for human therapy.

Main Methods:

• Constructed canine CARs targeting B7-H3 using a human-derived single-chain variable fragment (MGA271).
• Optimized CAR T-cell activation, transduction, and expansion methods.
• Assessed in vitro tumor killing using a 3D tumor spheroid assay and confirmed in vivo safety in healthy canines.

Main Results:

• Achieved high transduction efficacy, expansion, and in vitro tumor cell killing with canine B7-H3 CAR T-cells.
• Demonstrated that B7-H3 is a viable target for canine solid tumors, similar to human cancers.
• Confirmed the safety of the CAR T-cell treatment regimen in vivo, with no severe adverse events observed.

Conclusions:

• Successfully generated functional canine B7-H3-specific CAR T-cell products using a human-like production protocol.
• The developed canine model provides a safe and effective platform for preclinical evaluation of CAR T-cell therapies.
• This research offers a promising direction for establishing in vitro and in vivo models for both canine and human solid tumor immunotherapy.