Dinutuximab beta-targeted therapy kills beta-cell tumors of the pancreas

Abstract

Abstract Purpose Dinutuximab beta is a monoclonal antibody used only in glioblastoma. Streptozotocin is an agent that is particularly toxic to pancreatic beta cells. Dinutuximab beta causes cytotoxicity through natural killer cells and neutrophils and shows effects. In this study, cytotoxicity was induced by streptozotocin without natural killer cells and neutrophils. Gaining the ability to show the effect of Dinutuximab beta without a natural killer was the first aim of this study. This will be especially important in cases where the immune system is deficient, such as cancer. The second aim of the study was to investigate the effects of Dinutuximab beta on cell viability and cell death in insulinoma under the conditions created. Methods The effect of Dinutuximab beta in the presence of natural killer cells in vivo was created by the application of Streptozotocin to Beta-cell tumors of the pancreas in vitro. The cell viability was determined with WST-1 assay. Reactive oxygen species were measured by using dichlorofluorescein diacetate as a spectrophotometer. The cells were marked with DAPI to indicate apoptotic markers (nuclear condensation and fragmentation) with the confocal microscope. GLUT2 (Glucose transporter 2), IR (Insulin receptor), INS1, and INS2 expression levels were analyzed with q-RT-PCR. Results The cell cytotoxicity was induced by Streptozotocin. The cells proliferated with the administration of Dinutuximab beta alone. The result of Dinutuximab beta administered following Streptozotocin administration resulted in more cell death, increased ROS levels, GLUT2, Ins1, and Ins2 mRNA expression levels, and decreased IR mRNA expression levels. Furthermore, the cells predominantly died via apoptosis showing cytoplasmic condensation and DNA fragmentation. Conclusions The lethal effect of Dinutuximab beta without a natural killer was provided by Streptozotocin in Beta cell tumors of the pancreas.