Endoscopic Ultrasound-Guided Fine Needle Injection of Immature Dendritic Cells into Advanced Pancreatic Carcinoma Refractory to Gemcitabine: A Pilot Study

Abstract

Background and Aim: Immunotherapy against cancer has been investigated using different type of immune cells and the crucial role of dendritic cells (DCs) for the induction of primary T-cell-dependent immune responses was established. Intratumorally injected immature DCs would acquire and process tumor antigens in situ, migrate to regional lymphoid organs, and initiate a significant tumor specific immune response. The aim of this pilot study is to determine the feasibility, safety and clinical response of endoscopic ultrasound (EUS)-guided fine needle injection (FNI) of immature DC into the pancreatic cancer that had progressed to a metastatic disease after repeated systemic administration of gemcitabine D. Patients and Methods: Six patients with unresectable pancreatic cancer that had been unsuccessfully treated with gemcitabine were enrolled: all 6 patients in stage IVb with multiple liver metastasis, in whom 2 with malignant ascites. Immature DCs were generated from peripheral monocytes of patients with granulocyte-macrophage-colony stimulating factor and interleukin-4. Patients received intratumoral injection of 10 billion or more immature DC at 2-3 sites using EUS-guided FNI. Physical and laboratory examinations were performed to assess potential vaccine toxicity. Clinical endpoints included CA 19-9, tumor response and survival. Results: All DC injections were well tolerated without any clinical toxicity. The level of CA19-9 was decreased in 3 patients, mixed responses was observed in 3 (2 with malignant ascites) and the median survival of patients was 8 months. Conclusion: Direct injection of immature DC into the pancreatic tumor resulted in the generation of a potent antitumor immune response as evidenced by decreased CA19-9 levels and prolonged survival. Therefore intratumoral DC injection is a viable alternative to peripheral DC vaccination therapy for unresectable pancreatic cancer.