4603

Novel anti-NKp46 for Treatment of Autoimmune Diseases and Cancer

Mandelboim Ofer, HUJI, School of Medicine - IMRIC, Immunology and Cancer Research

 

Category

Life Sciences and Bio Technology   

Keywords

Antibodies, NK cells

Current development stage

 TRL4 - POC & Safety of candidate drug formulation is demonstrated in defined animal model

Application

  • Natural killer (NK) cells are innate effector lymphocytes that efficiently kill tumor cells without prior stimulation. NK are crucial first responders to tumor transformation and viral, bacterial, or fungal infections. They are also involved in autoimmune diseases such as Type I and II Diabetes.
  • NKp46 is important activating receptor in NK cell. Its role in the identification and elimination of various NK cell targets. NKp46 function in various autoimmune diseases was established. In Type 1 Diabetes NKp46 was shown to kill beta cells and in type II Diabetes it was shown to affect macrophages polarization via the secretion of IFN.  NKp46 expression is elevated in NK cells found in the synovial fluids of RA patients. Finally expression of NKp46 is induced on NK and some T cell leukemia.   

Our Innovation

The researchers discovered Novel NKp46 antibodies for preventing and/or treating malignant and autoimmune diseases.

  • The antibodies enable to induce NKp46 internalization and degradation
  • The antibodies significantly affect NKp46 activity against NKp46-dependent targets demonstrating decreased killing of tumor cells, virally infected cells and pancreatic beta cells.
  • Toxin-conjugated antibody kills NKp46 positive tumors

Pre-Clinical Results

  • The finding uncovers that the human NKp46 receptor and its mouse homologue NCR-1 specifically recognize both human and murine pancreatic β-cells.
  • By using NKp46 knockout mice and the LDST model, it was shown that the development of diabetes is impaired in the absence of NKp46. 
  • It was demonstrated in vitro that the killing of β-cells derived from NOD mice is also NKp46 dependent.  Thus, NKp46 is a significant determinant in the progression from insulitis to diabetes.
  • Binding of the antibody induce NKp46 internalization. Useful for the killing of tumors expression NKp46.   

4603.jpg

FIGs. 1A-B are graphs illustrating that several novel anti-NKp46 mAbs bind NKp46. Figures show one representative experiment out of 6 performed; FIG. 1A: FACS staining using anti-NKp46 mAbs (commercial anti-NKp46, 4G1G1, hNKp46.02, hNKp46.09, hNKp46.12) and a control mAb (12E7) of BW parental versus BW transfected cells expressing NKp46 (black and red histograms, respectively). The filled gray histogram represents staining with secondary antibody only of the BW parental cells. The background of BW NKp46 transfectants was similar and is not shown in the figure. FIG. 1B: FACS staining using anti-NKp46 mAbs (commercial anti-NKp46, 4G1G1, hNKp46.02, hNKp46.09, hNKp46.12) and a control mAb (12E7) of IL-2 activated primary bulk human NK cells (black histogram). The filled gray histogram represents staining of NK cells with secondary antibody only.

Opportunity

  • Therapeutic drug for the treatment of NKp46-dependent autoimmune diseases, such as, Type 1 Diabetes and RA, and NK cell related malignancies.
  • Prevent the development of Type1 Diabetes and the life-long treatment of insulin. There is no equivalent type of drug to treatment of Type 1 Diabetes today which addresses the disease itself and not the symptoms (i.e insulin).  

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
+972-2-6586608
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