A NEW study has introduced an innovative approach to CAR-T (Chimeric Antigen Receptor T-cell) therapy that could address some of the current challenges in cancer treatment, such as high production costs and safety concerns associated with viral vectors. Traditional CAR-T therapies, which involve engineering T-cells to target and kill cancer cells, have shown remarkable potential in treating malignant tumours, particularly blood cancers. However, these therapies are often expensive and carry risks like insertional mutagenesis and secondary tumour formation.
The researchers developed a novel CAR-T engineering technique using mRNA delivered through lipid nanoparticles (LNPs), which offers a non-viral alternative to the traditional viral vector-based method. This approach not only reduces costs but also enhances safety, potentially eliminating some of the risks of viral-based methods. The team successfully used LNPs to deliver mRNA encoding full-human CAR constructs, which led to high levels of CAR expression and significant anti-tumour activity in laboratory tests.
In vitro experiments showed that the engineered CAR-T cells exhibited potent cytotoxicity against leukemic cells and increased cytokine secretion when co-cultured with Raji cells. These results were further validated in an in vivo model using mice with engrafted Raji tumour cells. The treated mice displayed marked tumour regression and prolonged survival, demonstrating the therapeutic efficacy of the mRNA-LNP CAR-T cells.
This innovative approach could revolutionise CAR-T therapy by offering a safer, more accessible treatment option. With the potential to reduce production costs and improve patient outcomes, mRNA-LNP-based CAR-T therapies may become a key component of future cancer immunotherapy strategies.
Helena Bradbury, EMJ
Reference
Chen Z et al. mRNA-laden lipid nanoparticle-enabled humanized CD19 CAR-T-cell engineering for the eradication of leukaemic cells. Br J Haematol. 2025;DOI: 10.1111/bjh.19988.
