Korean J Urol.  2007 Feb;48(2):111-119. 10.4111/kju.2007.48.2.111.

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

• Park DS
• Cho HJ
• Han MY
• Lee SJ
• Oh DY
• Hwang SK

• KMID: 2139747
• DOI: http://doi.org/10.4111/kju.2007.48.2.111

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.

Keyword

Carcinoma; renal cell; Vaccines

MeSH Terms

Antigen-Presenting Cells
Carcinoma, Renal Cell*
Colony-Stimulating Factors
Dendritic Cells*
Flow Cytometry
Follow-Up Studies
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Immunotherapy
Interleukin-2
Interleukin-4
Monocytes
Recurrence
Tissue Donors
Vaccination
Vaccines*
Colony-Stimulating Factors
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-2
Interleukin-4
Vaccines

Figure

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  Fig. 1 Monocyte purity after using a magnetic activated cell sorting column. (A) CD14-fluorescein isothiocyanate (FITC) isotype control. (B) CD14-FITC.

• 

  Fig. 2 Flow cytometric analysis of CD86 presenting dendritic cellular maturation before (A) and after (B) stimulation by autologous tumor vaccine and lipopolysaccharide.

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  Fig. 3 (A) Monocyte (CD14-FITC) of peripheral blood in days 0 (green) and 5 (purple) cultures. (B) Comparison of dendritic cellular maturation [(CD86-phycoerythrin (PE)] in days 5 (purple) and 7 (green) cultures.

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  Fig. 4 Flow cytometric analysis of CD86, with CD11c. (A) Analysis of a 5 day culture: bloating cells; 9.4% (right upper quadrant: mature dendritic cell) and 74.6% (right lower quadrant: immature dendritic cell). (B) Analysis of a 5 day culture: attached cells; 11.2% (right upper quadrant: mature dendritic cell), 34.4% (right lower quadrant: immature dendritic cell). (C) Analysis of a 7 day culture with 20ng of interleukin-4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF), mature dendritic cell (right upper quadrant): 80.2%. (D) Analysis of a 7 day culture with 10ng of IL-4 and GM-CSF, mature dendritic cell (right upper quadrant): 80.5%.

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  Fig. 5 Phenotype (flow cytometric analysis) of monocytes at day 0 (lower left, each) and 7 (lower right, each) in cultures with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), and after pulsing with autologous tumor vaccine: (A) CD14-FITC, (B) CD83-PE, (C) CD86-PE.

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