Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo

• DOI: 10.1073/pnas.0901653106
• Publication Date: 2009-06-27T02:02:10Z
• Authors: Caroline Sola; Pascale André; Céline Lemmers; Nicolas Fuseri; Cécile Bonnafous; Mathieu Bléry; Nicolai R. Wagtmann; François Romagné; Eric Vivier; Sophie Ugolini
• Keywords: Lymphokine-activated killer cell; Syngenic; NK-92

Natural killer (NK) cells are lymphocytes of the innate immune system able to recognize and kill tumors lacking self-MHC class I molecules. This “missing-self” recognition is mediated by lack engagement MHC I-specific inhibitory NK cell receptors that include Ig-like (KIR) in humans Ly49 molecules mice. A promising immunotherapeutic strategy against + cancer block using monoclonal antibodies (mAb). However, interactions between their also required for acquisition functional competence, a process referred as “education.” In addition, involved self-tolerance on educated cells. Here, we developed preclinical mouse model which all single transgenic receptor, human KIR2DL3, through with its HLA-Cw3 ligand. approach revealed could be reprogrammed control development syngenic vivo. Moreover, vivo anti-KIR mAb treatment induced killing HLA target without breaking self-tolerance. Finally, long-term infusion neither abolished education nor tumor recognition. Therefore, these results strongly support use receptor blockade patients.