Generation and preclinical characterization of a Fc-optimized GITR-Ig fusion protein for induction of NK cell reactivity against leukemia.

ABSTRACT: Natural killer (NK) cells are cytotoxic lymphocytes that largely contribute to the efficacy of therapeutic strategies like allogenic stem cell transplantation in acute myeloid leukemia (AML) and application of Rituximab in chronic lymphocytic leukemia (CLL). The tumor necrosis factor (TNF) family member GITR ligand (GITRL) is frequently expressed on leukemia cells in AML and CLL and impairs the reactivity of NK cells which express GITR and upregulate its expression following activation. We developed a strategy to reinforce NK anti-leukemia reactivity by combining disruption of GITR-GITRL interaction with targeting leukemia cells for NK antibody-dependent cellular cytotoxicity (ADCC) using GITR-Ig fusion proteins with modified Fc moieties. Neutralization of leukemia-expressed GITRL by the G

SUBMITTER: Schmiedel BJ 

PROVIDER: S-EPMC3616539 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature