Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells

Purpose: Dendritic cells are the most potent stimulators of immune response s including antitumor responses. We performed a pilot study of cultured ant igen loaded dendritic cells in patients with metastatic renal cell carcinom a. Materials and Methods: Dendritic cells were obtained by culturing plastic a dherent mononuclear cells from peripheral blood for 5 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Day 5 dendritic cells were loaded with cell lysate from cultured autologous tum or cells and with the immunogenic protein keyhole-limpet hemocyanin (KLH) w hich serves as a helper antigen and as a tracer molecule. During the antige n pulse dendritic cells were activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Dendritic cells were administered by 3 intravenous infusions at monthly intervals. Cellular and humoral immune res ponses to KLH and cell lysate were measured in vitro before and after the v accinations. Results: Preparation of 12 dendritic cell vaccines from patients with advan ced renal cell carcinoma was successful. Treatment with fully activated CD8 3(+) dendritic cells was well tolerated with moderate fever as the only sid e effect. Potent immunological responses to KLH and, most importantly, agai nst cell lysate could be measured in vitro after the vaccinations. Conclusions: Our data demonstrate that a dendritic cell based vaccine can i nduce antigen specific immunity in patients with metastatic renal cell carc inoma. Dendritic cell based immunotherapy represents a feasible, well toler ated and promising new approach for the treatment of advanced renal cell ca rcinoma.