CRISPR/Cas9 basierte Differenzierung von mit CARs ausgestatteten Zellen mit NK-Zelleigenschaften für die Behandlung der akuten myeloischen Leukämie
Zusammenfassung der Projektergebnisse
Chimeric antigen receptor (CAR)-induced suppression of the transcription factor B cell CLL/lymphoma 11B (BCL11B) propagates CAR-induced killer (CARiK) cell development from lymphoid progenitors. We showed that CRISPR/Cas9-mediated Bcl11b knockout in human and murine early lymphoid progenitors distinctively modulates this process either alone or in combination with a CAR. Upon adoptive transfer into hematopoietic stem cell recipients, Bcl11b-edited progenitors mediated innate-like antigen-independent anti-leukemic immune responses. With CAR expression allowing for antigen-specific responses, double-edited lymphoid progenitors acquired adaptive NK cell functions such as clonal expansion, persistence, and recall responses. These findings give important insights into how Bcl11b-targeting can be used to tailor anti-leukemia functionality of CAR-engineered lymphoid progenitor cells.
Projektbezogene Publikationen (Auswahl)
-
Targeting BCL11B in CAR-engineered lymphoid progenitors drives NK-like cell development with prolonged anti-leukemic activity. Molecular Therapy, 33(4), 1584-1607.
Baatz, Franziska; Ghosh, Arnab; Herbst, Jessica; Polten, Saskia; Meyer, Johann; Rhiel, Manuel; Maetzig, Tobias; Geffers, Robert; Rothe, Michael; Bastone, Antonella Lucia; John-Neek, Philipp; Frühauf, Jörg; Eiz-Vesper, Britta; Bonifacius, Agnes; Falk, Christine S.; von Kaisenberg, Constantin; Cathomen, Toni; Schambach, Axel; van den Brink, Marcel R.M. ... & Sauer, Martin G.
