A phase I study of immunotherapy with tumor cell-dendritic cell fusion vaccine in patients with advanced or recurrent gastrointestinal cancer

Abstract

2615 Background: Immunotherapy with tumor cell-dendritic cell fusion vaccine has been shown to induce the immune response against multiple tumor antigens including unknown tumor antigens. The aim of this study was to test safety, feasibility, and clinical response of immunotherapy with tumor cell-dendritic cell fusion vaccine. Methods: Nine patients with advanced or recurrent gastrointestinal cancer that is unresponsive to standard surgical therapy and chemotherapy were enrolled in this study after informed consent was obtained. Monocytes were separated from the peripheral blood by leukapheresis and were cultured with GM-CSF and IL-4 for 6 days. Then TNFα, IL-1β, IL-6, and PGE2 were added for maturation of dendritic cells. Fusion of irradiated tumor cells and dendritic cells was created by polyethylene glycol and electroporation. Fusion vaccine was subcutaneously injected in the inguinal region four times every two weeks. Safety and adverse effects were evaluated after vaccination. Delayed hypersensitivity skin-test, cytokine array, Th1/Th2, Tc1/Tc2, and clinical response were compared before and after vaccination. Results: There were neither adverse effects nor autoimmune responses after vaccination in all the patients. Delayed skin tests became positive in six of nine patients after vaccination. Th1/Th2 balance and Tc1/Tc2 balance were improved in six of nine patients after vaccination. IAP levels were decreased in five patients after vaccination. Clinical response was stable disease in five patients and progressive disease in four patients. Conclusions: Safety and feasibility of immunotherapy with tumor cell-dendritic cell fusion vaccine were confirmed in patients with advanced or recurrent gastrointestinal cancer by this study. No significant financial relationships to disclose.