Systemic delivery of CBT-15G DCLK1-targeted monoclonal antibody dramatically decreases tumorigenesis in a xenograft model of pancreatic cancer

摘要: IntroductionPancreatic cancer is the 4th leading cause of cancer mortality in the US. Treatments for pancreatic cancer are desperately needed as current drugs lead to little or no improvement in patient survival. Doublecortin-like kinase 1 (DCLK1) marks putative stem cells in colon and pancreatic cancers and regulates important oncogenic processes including epithelial-mesenchymal transition, which supports metastasis. DCLK1's extracellular domain is a novel target for therapeutic monoclonal antibodies (mABs) that has not previously been pursued.Materials and MethodsDevelopment of a DCLK1-targeted mAB: Balb/c mice were immunized with proprietary KLH-linked peptides targeting the DCLK1 extracellular domain. After immunization, mice were killed and spleens were taken and used to generate hybridoma cell lines, which were subcloned to the monoclonal level. Hybridoma media containing DCLK1-mAB …