A phase I/II study of vaccination with tumor-lysate pulsed dendritic cells in patients with metastatic renal cell cancer

Kaiser, L. Ph.D. Dendrimun GmbH, D-Aschaffenburg; Rebmann, U. Prof. department of urology, hospital Diakonissenanstalt, D-Dessau; Roigas, J. MD , department of urology, university hospital Charite, D-Berlin

e-mail: dendrimun@t-online.de

Dendritic cells are the most potent stimulators of immune response including antitumor-responses. We performed a phase I/II study of cultured antigen pulsed dendritic cells in patients with progressive metastatic renal cell carcinoma. Autologous dendritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 7 days in the presence of GM-CSF and IL-4. On day 7 dendritic cells were loaded with cell lysate (1:1) from autologous tumor cells. After antigen pulse dendritic cells were matured by a combination of tumor necrosis factor-alpha, prostaglandin E2, interleukin-6 and interleukin-1beta. On day 9 pulsed and matured dendritic cells with typical morphology (veils) were harvested. All preparations were done under GMP. Either dendritic cells were sent to hospital for application or cryopreseved for later use. Surface expression of fully matured dendritic cells were: HLA-DR, CD80, CD86, CD93, CD1a and nearly negative for CD14.

The final dendritic cell vaccine contains at least 5 x 10(6) dendritic cells plus the immunogeneic protein keyhole-limpet hemocyanin (KLH). Dendritic cells were injected into inguinal lymph nodes; 6 injections are scheduled with 4 weeks intervall.18 patients have entered the study so far. 4 CR , 3 PR, 4S D and 7 PD. Patient characteristics and details will be discussed. Vaccination was administered on an outpatient basis and was well tolerated in all patients. No clinical signs of autoimmune diesease were observed