2. Academic Validation
  3. mRNA-laden lipid nanoparticle-enabled humanized CD19 CAR-T-cell engineering for the eradication of leukaemic cells

mRNA-laden lipid nanoparticle-enabled humanized CD19 CAR-T-cell engineering for the eradication of leukaemic cells

  • Br J Haematol. 2025 Feb;206(2):628-643. doi: 10.1111/bjh.19988.
Zhaozhao Chen 1 2 3,  Anqi Ren 1 2 3,  Yingying Li 1 2 3,  Jinhui Shu 1 2 3,  Jianghua Wu 1 2 3,  Hekuan Huang 1 2 3,  Jingming Wang 1 2 3,  Yu Hu 1 2 3,  Heng Mei 1 2 3
Affiliations

Affiliations

  • 1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 2 Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, China.
  • 3 Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
PMID: 39761676 DOI: 10.1111/bjh.19988
Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has shown transformative potential in treating malignant tumours, with increasing global approval of CAR-T products. However, high-production costs and risks associated with viral vector-based CAR-T cells-such as insertional mutagenesis and secondary tumour formation-remain challenges. Our study introduces an innovative CAR-T engineering approach using mRNA delivered via lipid nanoparticles (LNPs), aiming to reduce costs and enhance safety while maintaining strong anti-tumour efficacy. We developed an LNP-based transfection protocol for efficient delivery of mRNA encoding full-human CAR constructs, achieving high CAR expression and significant cytotoxicity against leukaemic cells in vitro. Co-culture with Raji cells showed increased cytokine secretion and tumour cell killing by mRNA-LNP CAR-T cells. Therapeutic efficacy was further demonstrated in an NOD-scid-IL2Rγnull (NSG) mouse model with Raji engraftment, where treated mice exhibited marked tumour regression and extended survival. These findings underscore the potential of mRNA-LNPs as a non-viral, effective CAR-T engineering platform, offering a promising alternative to traditional methods that could improve CAR-T safety, efficacy and accessibility in clinical Cancer Immunotherapy.

Keywords

CAR‐T cells; Leukaemia eradication; mRNA‐LNP; non‐viral transfection.

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