Phase I clinical trial of hybrid cell vaccination in patients with gastrointestinal cancer.

2579 Background: Vaccination with hybrid cells of dendritic cells (DCs) and tumor cells can induce specific ant-tumor immunity against multiple tumor antigens including those that are unknown. We report the results of phase I study of hybrid cell vaccines comprised of autologous DC and autologous tumor cells in patients with Stage IV or recurrent gastrointestinal cancer.,Thirteen patients with Stage IV or recurrent gastrointestinal cancer were enrolled in this study after informed consent was obtained. Tumor cells were cryopreserved following acquisition from the primary or a metastatic site. DCs were induced from mononuclear cells of patients by culture with cytokines (6 days culture with GM-CSF and IL-4, and a further 1 day culture with TNF-α, IL-1 β, IL-6 and PGE2). Fusion of irradiated tumor cells and DC was created with a combination of PEG and electrofusion (two-step fusion method). At 2 week interval, patients received 4 freshly prepared fusion vaccines, with a constant dose range of 1 × 107 to 4 × 107 cells. The endpoints of this study were assessments of safety, anti-tumor immune response and clinical response.,Serious adverse events were not observed in any of the enrolled patients and all Common Toxicity Criteria were grade I. Clinical responses are 1 with partial response (PR), 5 with stable disease (SD) and 7 with progressive disease (PD). Delayed skin tests changed to positive in 5 patients. In patients with PR and SD, a shift to Th1 in Th1/Th2 balance of lymphocytes (IFN γ/IL10, IFN γ/IL4) was demonstrated by ELISPOT and cytokine flow cytometry analysis. After vaccination, decrease of immunosuppressive factors (IAP, TGF-β) in serum were shown in patients with PR and SD. There was no significant differences of CD4CD25 cells by vaccination.,These results suggests that a strategy of hybrid cell vaccine employing auto-DCs and auto-tumor cells is feasible in patients with gastrointestinal cancer and may show evidence of anti-tumor immune response. No significant financial relationships to disclose.