Chimeric mAb5E6 decreased the colony formation ability (50%) and migration (~40%) of MUC16 expressing pancreatic cancer cell lines. Besides, chimeric mAb 5E6 treated pancreatic cancer cells showed reduction in FAK and Akt signaling associated with tumorigenesis and migration...Genetically engineered anti-MUC16 antibody decreased the tumorigenicity of pancreatic cancer cells. Our data validated testing the novel anti-MUC16 chimeric antibody for payload delivery and therapeutic targeting in pancreatic cancer.