Gurney M, O'Reilly E, Corcoran S, et al. Concurrent Transposon Engineering and CRISPR/Cas9 Genome Editing of Primary CLL-1 Chimeric Antigen Receptor-Natural Killer Cells. Cytotherapy. 2022; 24 (11): 1087 (doi: 10.1016/j.jcyt.2022.07.008).
A combination of technologies paved the way for DNA transposon-based production of primary, donor-derived chimeric antigen receptor (CAR)-natural killer (NK) cells, which subsequently demonstrated action against a key antigen target in acute myeloid leukemia (AML). DNA transposons are versatile, non-viral gene vectors, and researchers used the TcBuster system for their engineering approach. They paired the system with Nanoplasmid technology and an Epstein-Barr virus-transformed lymphoblastoid feeder cell. Collectively, the approaches generated clinical-quality levels of CAR expansion and NK-cell expansion potential. The CAR-NK cells that resulted targeted C-type lectin-like molecule-1 (CLL-1), a prominent AML immunotherapeutic antigen also expressed by leukemia stem cells. Cell functionality improved when the protocol was adjusted for concurrent knockout of the NK cell checkpoint cytokine-inducible SH2-containing protein, using CRISPR/Cas9. The researchers say the work supports the potential role of DNA transposons in creating genome-edited NK cell products, which promise to enhance the inherent and alloreactive anti-tumor potential of NK cell adoptive transfer.
Tags: AML, patient care, transplantation, Treatment, Research, Cord Blood, Transplant, cell therapy, CAR T-cell, researchers, acute myeloid leukemia