German researchers have announced a new approach to improve immunotherapy for acute myeloid leukaemia (AML).
The scientists said they have conducted successful laboratory experiments to achieve “complete” switch-off of an important immune checkpoint for natural killer (NK) cells.
This was achieved using CRISPR/Cas gene editing to disrupt the KLRC1 gene, alongside modifying the NK cells to carry a chimeric antigen receptor (CAR) to target CD33. Tests on AML cells showed this prevented cancer cells from becoming resistant to the CAR-NK therapy.
The researchers write: “The development of CAR products for the treatment of AML is more challenging due to the disease heterogeneity and lack of AML-exclusive antigens.”
Reporting in Nature Communications, they say their doubly-modified CAR-NK cells were more able to destroy AML patient cancer cells, compared with NK cells only carrying the CAR receptor, or those only lacking the immune checkpoint.
Studies on mice carrying AML cells derived from patients showed that the doubly-modified CAR-NK cells led to significantly improved survival. The researchers, led by Professor Evelyn Ullrich of Universitaetsmedizin Frankfurt, say the next step is to establish if the modified cells might work in humans.
Researcher Tobias Bexte, of Goethe-Universität Frankfurt, said: “It is particularly promising that our double-modified NK cells even worked against cancer cells whose molecular profile is often associated with increased resistance to therapy.”
Source:
Bexte T, Albinger N, Al Ajami A, Wendel P, Buchinger L, Gessner A, Alzubi J, Särchen V, Vogler M, Rasheed HM, Jung BA, Wolf S, Bhayadia R, Oellerich T, Klusmann JH, Penack O, Möker N, Cathomen T, Rieger MA, Imkeller K, Ullrich E. (2024) “CRISPR/Cas9 editing of NKG2A improves the efficacy of primary CD33-directed chimeric antigen receptor natural killer cells.” Nature Communications, 30 September 2024, doi: 10.1038/s41467-024-52388-1.
Link: https://www.nature.com/articles/s41467-024-52388-1
Disclaimer: The news stories shared on this site are used as a way to inform our members and followers of updates and relevant information happening in Haematology. The BSH does not endorse the content of news items from external sources, and is not in a position to verify the findings, accuracy or the source of any studies mentioned. Any medical or drugs information is provided as an information resource only, and is not to be relied on for any diagnostic or treatment purposes.
News service provided by Englemed News.