Vaccination with DC/RCC fusions following cytoreductive nephrectomy.

Abstract

2511 Background: We have developed a cancer vaccine in which patient (pt) derived tumor cells are fused with autologous dendritic cells (DCs). In pts with metastatic renal cell carcinoma (mRCC), cytoreductive nephrectomy (CRN) has been associated with improved overall survival, potentially due to the reduction of tumor-mediated immunosuppression, and may therefore be a setting in which response to vaccination is enhanced. Methods: We conducted a phase I trial in which pts with mRCC undergo vaccination with autologous DC/RCC fusions following CRN. An initial cohort underwent vaccination with DC/RCC fusions alone and a subsequent cohort underwent vaccination in conjunction with GM- CSF. RCC were isolated from CRN specimens and were cryopreserved. DCs were generated from adherent mononuclear cells isolated from leukapheresis collections cultured for 5 days with GM-CSF and IL-4 and matured with TNFa for 48-72 hours. Vaccine was provided via sq injection at 3 wk intervals with tumor assessment via RECIST at wk 12. Results: 29 patients have been enrolled and 16 vaccinated. The mean yield of DCs was 164 × 106 with a mean viability of 81%. At time of fusion, mean RCC yield was 95 × 106 cells with a mean viability of 80%. Fusion cells were quantified by determining the percentage of cells that coexpressed unique DC and RCC antigens following coculture of RCC and DCs with polyethylene glycol. Mean fusion efficiency, viability, and vaccine dose was 26%, 81%, and 3.1 × 106 fusion cells, respectively. DC/RCC fusions potently stimulated allogeneic T cell proliferation ex vivo (mean stimulation indexes of 94, 44, and 10 for the DC, fusion and RCCs, respectively). Adverse events related to vaccination were largely restricted to injection site reactions. All pts in the initial cohort undergoing evaluation demonstrated vaccine induced anti-tumor immunity as defined by a 2 fold increase in IFNg expression by CD4 and/or CD8 T cells in response to ex vivo exposure to autologous tumor lysate. 3 pts demonstrated a partial response, and 4 have stable disease lasting 5, 8, 11, and 18 months following initiation of vaccination. Conclusions: Vaccination with DC/RCC fusions following nephrectomy is feasible, well tolerated, and associated with immunologic and clinical responses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genzyme