Development and Application of Mixed Vaccines in Renal Cell Carcinoma: Combining Autologous Tumor Cells with Dendritic Cells Derived from Autologous or Allogeneic Origin / 대한비뇨기과학회지

ABSTRACT

PURPOSE: To evaluate the effects of autologous tumor vaccine alone or in combination with dendritic cell vaccines, as a method of stimulating antigen-presenting cells in patients with a locoregionally confined renal cell carcinoma (RCC) or metastatic disease. MATERIALS AND METHODS: Twenty-seven patients with RCC pathological stages II to IV were treated with autologous tumor cell vaccine, either with or without dendritic cell vaccine. Interleukin 2 (IL-2) based immunotherapy was also applied to the patients with metastatic disease. Immunomagnetic beads were used to isolate CD14+ monocytes from patient or donor in dendritic cell preparations. IL-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) were used for maturation of dendritic cells. Flow cytometry evaluations were performed for dendritic cell maturation and changes in the immunological profiles following our treatment. RESULTS: Both the isolation of CD14+ monocyte, using Immunomagnetic beads, and the maturation of dendritic cells, using IL-4 and GM-CSF stimulation, were effective. Tumor immunological profiles showed increased CD3 and CD56 populations after treatment. Side effects related with vaccine were minimal and tolerable. Patients were stratified by the purpose for the vaccination; 8 patients for post-nephrectomy adjuvant therapy and 19 for adjuvant immunotherapy of a metastatic disease. All 8 patients in the former showed a disease free state, while only one of the 19 in the latter group remained in complete remission, while 6 showed short-term responses. CONCLISIONS Autologous RCC vaccine, combined with or without dendritic cell vaccine, might be effective in the suppression of tumor recurrence in locoregionally confined RCC, although a longer follow-up will be required. These vaccines should be further developed to reach their therapeutic purpose in metastatic RCC.