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

Published

Journal Article

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-alpha. DCs were fused to patient derived RCC with serial electrical pulses. Patients received up to 3 vaccinations at a fixed dose of 4x10(7) to 1x10(8) 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-gamma 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.

Full Text

Duke Authors

Cited Authors

  • Avigan, DE; Vasir, B; George, DJ; Oh, WK; Atkins, MB; McDermott, DF; Kantoff, PW; Figlin, RA; Vasconcelles, MJ; Xu, Y; Kufe, D; Bukowski, RM

Published Date

  • October 2007

Published In

Volume / Issue

  • 30 / 7

Start / End Page

  • 749 - 761

PubMed ID

  • 17893567

Pubmed Central ID

  • 17893567

International Standard Serial Number (ISSN)

  • 1524-9557

Digital Object Identifier (DOI)

  • 10.1097/CJI.0b013e3180de4ce8

Language

  • eng

Conference Location

  • United States