CRISPR-Cas9 based gene editing of the immune checkpoint NKG2A enhances NK cell mediated cytotoxicity against multiple myeloma

Abstract: Natural Killer (NK) cells are known for their high intrinsic cytotoxic capacity, and the possibility to be applied as ‘off-the-shelf’ product makes them highly attractive for cell-based immunotherapies. In patients with multiple myeloma (MM), an elevated number of NK cells has been correlated with higher overall-survival rate. However, NK cell function can be impaired by upregulation of inhibitory receptors, such as the immune checkpoint NKG2A. Here, we developed a CRISPR-Cas9-based gene editing protocol that allowed us to knockout about 80% of the NKG2A-encoding killer cell lectin like receptor C1 (KLRC1) locus in primary NK cells. In-depth phenotypic analysis confirmed significant reduction in NKG2A protein expression. Importantly, the KLRC1-edited NK cells showed significantly increased cytotoxicity against primary MM cells isolated from a small cohort of patients, and maintained the NK cell-specific cytokine production. In conclusion, KLRC1-editing in primary NK cells has the prospect of overcoming immune checkpoint inhibition in clinical applications

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• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: OncoImmunology. - 11, 1 (2022) , 2081415, ISSN: 2162-402X

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2022
• Creator: Bexte, Tobias ; Alzuʾbi, Jamal ; Reindl, Lisa Marie ; Wendel, Philipp ; Schubert, Ralf ; Salzmann-Manrique, Emilia ; Metzler, Ivana von ; Cathomen, Anton ; Ullrich, Evelyn

Further information

• DOI: 10.1080/2162402x.2022.2081415
• URN: urn:nbn:de:bsz:25-freidok-2275842
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.