Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma

David E. Avigan, Baldev Vasir, Daniel J. George, William K. Oh, Michael B. Atkins, David F. McDermott, Philip W. Kantoff, Robert A. Figlin, Michael J. Vasconcelles, Yuanxin Xu, Donald Kufe, Ronald M. Bukowski

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103 Scopus citations

Abstract

In the present study, we assessed the feasibility, toxicity, immunologic response, and clinical efficacy of vaccination with allogeneic dendritic cell (DC)/tumor fusions in patients with metastatic renal cell carcinoma (RCC). Patients with stage IV RCC with accessible tumor lesions or independent therapeutic indications for nephrectomy were eligible for enrollment. Tumors were processed into single cell suspensions and cryopreserved. DCs were generated from adherent peripheral blood mononuclear cells isolated from normal volunteers and cultured with granulocyte macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α. DCs were fused to patient derived RCC with serial electrical pulses. Patients received up to 3 vaccinations at a fixed dose of 4×10 to 1×10 cells administered at 6-week intervals. Twenty-four patients underwent vaccination. Twenty-one and 20 patients were evaluable for immunologic and clinical response, respectively. DCs demonstrated a characteristic phenotype with prominent expression of HLA class II and costimulatory molecules. A mean fusion efficiency of 20% was observed, determined by the percent of cells coexpressing DC and tumor antigens. No evidence of significant treatment related toxicity or auto-immunity was observed. Vaccination resulted in antitumor immune responses in 10/21 evaluable patients as manifested by an increase in CD4 and/or CD8 T-cell expression of interferon-γ after ex vivo exposure to tumor lysate. Two patients demonstrated a partial clinical response by Response Evaluation Criteria in Solid Tumors criteria and 8 patients had stabilization of their disease. Vaccination of patients with RCC with allogeneic DC/tumor fusions was feasible, well tolerated, and resulted in immunologic and clinical responses in a subset of patients.

Original languageEnglish
Pages (from-to)749-761
Number of pages13
JournalJournal of Immunotherapy
Volume30
Issue number7
DOIs
StatePublished - Oct 2007
Externally publishedYes

Keywords

  • Dendritic cell tumor fusion
  • Renal cell carcinoma
  • Tumor immunotherapy

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