In this work, we describe the potential of NK cells to target patient-derived primary pancreatic cancer organoids in a 3D setting and show that the NK cell cytotoxic potential against pancreatic cancer organoids can be enhanced by using clinically available monoclonal antibodies with the ability to trigger ADCC by targeting of HER2 and PD-L1. The gene discussed is ERBB2; the disease is familial pancreatic carcinoma.