title: Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma.
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-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.
authors: Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. davigan@bidmc.harvard.edu
authors: David E
authors: DE
authors: Avigan
authors: Baldev
authors: B
authors: Vasir
authors: Daniel J
authors: DJ
authors: George
authors: William K
authors: WK
authors: Oh
authors: Michael B
authors: MB
authors: Atkins
authors: David F
authors: DF
authors: McDermott
authors: Philip W
authors: PW
authors: Kantoff
authors: Robert A
authors: RA
authors: Figlin
authors: Michael J
authors: MJ
authors: Vasconcelles
authors: Yuanxin
authors: Y
authors: Xu
authors: Donald
authors: D
authors: Kufe
authors: Ronald M
authors: RM
authors: Bukowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor