Monoclonal Antibody Blocks Development of Type I Diabetes in Mouse Model

Monoclonal antibody treatment prevented development of type I diabetes in a mouse model of the disease.

Type 1 diabetes is caused by an autoimmune reaction that destroys the pancreatic beta cells that produce insulin. The disease, which is currently treated by lifetime injections of insulin, is marked by pathologically elevated levels of sugar in the blood and urine that cause high rates of morbidity and mortality.

Investigators at The Hebrew University of Jerusalem (Israel) had previously identified a link between development of type I diabetes and the NKp46 receptor on the surface of NK (natural killer) immune cells. The NKp46 receptor is a member of the primary activating receptors of NK cells. This receptor was shown to recognize pancreatic beta cells, leading to their destruction by the immune system.

In the current study the investigators evaluated the potential therapeutic use of a monoclonal antibody intended to block the NKp46 receptor. They reported in the February 26, 2015, online edition of the journal PLoS One that their NCR1.15 antibody recognized the mouse homologue protein of NKp46, named Ncr1, and was able to down-regulate the surface expression of the NKp46 receptor on primary murine NK cells following antibody injection in vivo. Additionally, NCR1.15 treatments were able to down-regulate cytotoxic activity mediated by NKp46, but not by other NK receptors.

The investigators examined type I diabetes development in two models, non-obese diabetic mice and mice with a model of diabetes caused by low-dose streptozotocin. Results showed a significantly lower incidence of diabetic mice in the NCR1.15-treated group compared to control groups.

The Hebrew University of Jerusalem has signed an exclusive license agreement with the clinical-stage biopharmaceutical company BioLineRx (Jerusalem, Israel) to develop and commercialize the drug BL-9020 (NCR1.15) for the treatment of type I diabetes.

Related Links:
The Hebrew University of Jerusalem
BioLineRx