Novel mRNA-Engineered Fully Human CAR-T Cells Targeting AXL in Solid Tumors

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• AXL receptor tyrosine kinase is a therapeutic target in solid tumors.
• Viral vector CAR-T cells have limitations like insertional mutagenesis and immunogenicity.
• There is a need for safer, scalable CAR-T cell therapies.

Purpose of the Study:

• To develop and evaluate mRNA-engineered fully human AXL CAR-T cells.
• To assess the safety and efficacy of this novel CAR-T platform.
• To provide a scalable alternative for solid tumor immunotherapy.

Main Methods:

• Generated mRNA-engineered fully human AXL CAR-T cells via electroporation.
• Quantified CAR expression and T-cell viability using flow cytometry.
• Assessed in vitro and in vivo antitumor activity in cancer models.

Main Results:

• Achieved high CAR expression (>90%) with preserved T-cell viability (>90%).
• Demonstrated dose-dependent cytotoxicity and antigen-specific cytokine secretion in vitro.
• Showed significant tumor growth suppression in vivo without adverse effects.

Conclusions:

• mRNA electroporation enables cost-effective, large-scale production of CAR-T cells.
• This platform eliminates risks associated with viral vectors, such as insertional mutagenesis and immunogenicity.
• mRNA-engineered fully human AXL CAR-T cells represent a promising, safer immunotherapy for solid tumors.