mRNA-Based Production of CAR NK Cells
Park HY, Kim SJ, Kim K, et al. Polyaspartamide-Mediated Messenger RNDA Delivery Enables Efficient Ex Vivo Engineering of Chimeric Antigen Receptor Natural Killer Cells via Enhanced Cellular Internalization. ACS Applied Materials & Interfaces. 2026; 18 (35) (doi: 10.1021/acsami.6c07623).
Researchers describe a new process that overcomes the limitations of established practices for manufacturing natural killer (NK) cells that express chimeric antigen receptors (CAR). Although the allogeneic potential of CAR NK cells is substantial, producing them is complex and time-intensive. Instead of using lentiviral or retroviral transduction to stabilize CAR expression, developers turned to CAR messenger RNA (mRNA). The simple, nonviral approach employs amphiphilic polyaspartamide-based polyplexes, derivatives of which promote efficient mRNA complexation, improved cellular uptake, and robust CAR expression in NK cell lines. Increased expression of cytotoxic mediators and cytokines allowed NK cells created with CAR–NKG2D mRNA to unleash powerful and selective cytotoxicity against multiple cancer cell lines without harming normal fibroblasts. Investigators tested the cells in a murine model of colon cancer, where they significantly suppressed tumor growth.