Human anti‐NKp46 antibody for studies of NKp46‐dependent NK cell function and its applications for type 1 diabetes and cancer research. Issue 2 (17th December 2018)

• Record Type: Journal Article
• Authors: Berhani, Orit; Glasner, Ariella; Kahlon, Shira; Duev‐Cohen, Alexandra; Yamin, Rachel; Horwitz, Elad; Enk, Jonatan; Moshel, Ofra; Varvak, Alexandar; Porgador, Angel; Jonjic, Stipan; Mandelboim, Ofer
• Is Part Of: European journal of immunology. Volume 49:Issue 2(2019)
• Page Start: 228
• Page End: 241
• Publication Date: 2018-12-17
• Subjects: NK cells -- NKp46 -- antibody -- cancer -- type 1 diabetes; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847611
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Natural killer (NK) cells are innate lymphocytes that efficiently eliminate cancerous and infected cells. NKp46 is an important NK activating receptor shown to participate in recognition and activation of NK cells against pathogens, tumor cells, virally infected cells, and self‐cells in autoimmune conditions, including type I and II diabetes. However, some of the NKp46 ligands are unknown and therefore investigating human NKp46 activity and its critical role in NK cell biology is problematic. We developed a unique anti‐human NKp46 monocloncal antibody, denoted hNKp46.02 (02). The 02 mAb can induce receptor internalization and degradation. By binding to a unique epitope on a particular domain of NKp46, 02 lead NKp46 to lysosomal degradation. This downregulation therefore enables the investigation of all NKp46 activities. Indeed, using the 02 mAb we determined NK cell targets which are critically dependent on NKp46 activity, including certain tumor cells lines and human pancreatic beta cells. Most importantly, we showed that a toxin‐conjugated 02 inhibits the growth of NKp46‐positive cells; thus, exemplifying the potential of 02 in becoming an immunotherapeutic drug to treat NKp46‐dependent diseases, such as, type I diabetes and NK and T cell related malignancies. Abstract : NK cells express a wide variety of receptors, critical in balancing NK cell activity. The NKp46 receptor participates in the elimination of harmful target cells. We developed a novel multifunctional antibody aimed to study NKp46 biology and to treat NKp46 expressing cancers and diseases, such as type 1 diabetes.