Interim safety and efficacy results from a phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma

Abstract

2526 Background: Vaccination with dendritic cell (DC)/tumor cell fusions can induce specific anti-tumor immunity in preclinical studies and has shown clinical activity. We report results of a fully enrolled, ongoing phase I/II study of electrofusion vaccine (EFV), comprised of allogeneic DCs (alloDC) and autologous tumor-derived cells administered subcutaneously to patients with Stage IV renal cell carcinoma (RCC). Methods: Tumors were processed and cryopreserved following acquisition from the primary or a metastatic site. Volunteer donor peripheral blood mononuclear cells were used to generate alloDC. At 6 week intervals, patients received up to 3 freshly prepared, irradiated EFV, within a constant dose range of 4 x 107 to 1 x 108 total cells. Study endpoints were safety, and tumor and immunologic response assessments. Results: Of the 30 enrolled patients, data are available on 21; 19 of the 21 were eligible for vaccination. The median age is 58 years (12 M, 9 F); mean number of metastatic sites is 2.4. Fifteen patients received prior treatments, including high dose IL-2. The mean fusion efficiency for 50 vaccine preparations is 20.7%, as determined by cell coexpression of specific DC and tumor markers. The only serious adverse event (excessive intraoperative bleeding) considered related to the study occurred during a tumor acquisition procedure. Adverse events assessed by the investigators as related to EFV and occurring in more than 1 patient were injection site reactions (n=5), fatigue (n=3) and coughing (n=3), all Common Toxicity Criteria grade I or II. Tumor responses to date (9 patients) are 1 partial response, 3 stable disease. Complete analyses of safety, immunologic reactivity (autologous tumor-induced delayed-type hypersensitivity and intracellular interferon γ production) and tumor response assessments will be presented. Conclusions: These interim data suggest a vaccination strategy employing alloDC electrofused with tumor-derived cells in patients with Stage IV RCC is feasible, well-tolerated and may show evidence of tumor response. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dana-Farber Cancer Institute; Genzyme Corp. Genzyme Corp. Genzyme Corp. Genzyme