mRNA-Engineered CAR-T Cells Show Promise in Treating Solid Tumors

Strategic Insights -

Researchers from Sun Yat-sen University in Shenzhen, China, have made significant advancements in the development of mRNA-engineered CAR-T cells, a potential game-changer in the treatment of solid tumors. This innovative approach eliminates the risks of insertional mutagenesis and immunogenicity associated with traditional viral vector-based therapies. The study, published in Biomedicines, demonstrated the effectiveness of this platform in suppressing tumor growth in a lung cancer xenograft mouse model.

Key Takeaways:

  • The AXL receptor tyrosine kinase is a promising therapeutic target in solid tumors, and mRNA-engineered CAR-T cells may offer a safer and more scalable alternative to traditional viral vector-based approaches.
  • Researchers used an mRNA-electroporated platform to generate fully human AXL CAR-T cells, which exhibited high CAR expression and preserved T-cell viability in vitro and in vivo.
  • The study demonstrated dose-dependent cytotoxicity and antigen-specific cytokine secretion by [superscript]mfhAXL CAR-T cells in vitro.
  • In vivo, the administration of [superscript]mfhAXL CAR-T cells suppressed tumor growth without body weight loss in a lung cancer xenograft mouse model.
  • The mRNA-electroporated [superscript]mfhAXL CAR-T platform enables cost-effective, large-scale production, offering a safer alternative to viral vector-based approaches.
  • Key researchers involved in this study include Bo Zou, Mengge Wang, Shimeng Bai, Ning Li, Zhongyi Fan, Yuanzheng Peng, Mingshu Han, Chen Zeng, Hongzhou Lu, Lin Qi, Xingding Zhang, Xiaohua Tan, and Qibin Liao.

Statistics:

  • 90% CAR expression at 24 hours post-transfection, as measured by flow cytometry.
  • 90% T-cell viability post-transfection, as measured by flow cytometry.
  • Dose-dependent cytotoxicity in vitro, with up to 80% cell killing at the highest dose.
  • Significant suppression of tumor growth in vivo, with a 60% reduction in tumor volume over 14 days.

Sources:

  • Biomedicines, 2025,13(4):844 (https://doi-org.sdpl.idm.oclc.org/10.3390/biomedicines13040844)
  • Sun Yat-sen University, Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus, Shenzhen 518106, People's Republic of China