Dinutuximab Beta-Targeted Immunotherapy Kills Pancreatic Beta Cell Tumors

Abstract Dinutuximab beta is the first monoclonal antibody that used for the treatment of neuroblastoma. The aim of this study is to investigate the effects of Dinutuximab beta, whose effect is unknown in pancreatic beta cell tumor, based on the similarity between pancreatic beta cells and neurons. We have used insulinoma INS-1 cells. Dinutuximab beta (Qarziba®) which presented by EUSA Pharma was used for the experiments. The cell cytotoxicity was induced by STZ. Dinutuximab beta was administered to the cells following STZ administration and before STZ administration. The cell viability with WST-1 assay, reactive oxygen species by using dichlorofluorescein diacetate were measured. The cells were marked with DAPI to indicate apoptotic markers with confocal microscope. GLUT2, IR, Ins1 and Ins2 expression levels were analyzed with q-RT-PCR. The INS-1 cells proliferated with administration of Dinutuximab beta alone. The result of Dinutuximab beta administered following STZ administration, resulted in more cell death, increased ROS levels, GLUT2, Ins1, Ins2 gene expression levels and decreased IR gene expression levels than Dinutuximab beta administered before STZ administration. After Dinutuximab beta was administered to the cells following STZ administration, the cells predominantly died via apoptosis showing cytoplasmic condensation and DNA fragmentation after 24 and 48 hours. As a result, Dinutuximab beta can show its effect after occurring toxicity. Time-dependent cell death increases as a result of administration of Dinutuximab beta after toxicity induced by STZ in insulinoma cells. Its use as a chemotherapeutic agent in tumor treatment should be supported by in vivo studies.