Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma

• Published in: Blood Vol. 117; no. 2; pp. 393 - 402
• Main Authors: Rosenblatt, Jacalyn, Vasir, Baldev, Uhl, Lynne, Blotta, Simona, MacNamara, Claire, Somaiya, Poorvi, Wu, Zekui, Joyce, Robin, Levine, James D., Dombagoda, Dilani, Yuan, Yan Emily, Francoeur, Karen, Fitzgerald, Donna, Richardson, Paul, Weller, Edie, Anderson, Kenneth, Kufe, Donald, Munshi, Nikhil, Avigan, David
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 13.01.2011; Americain Society of Hematology; American Society of Hematology
• Series: Clinical Trials and Observations
• Subjects: Adult; Aged; Antibodies, Protozoan - immunology; Antigens, Protozoan - immunology; Biological and medical sciences; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Fusion; Clinical Trials and Observations; Dendritic Cells - immunology; Female; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunotherapy - methods; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Multiple Myeloma - immunology; Multiple Myeloma - therapy; Antineoplastic agent; Human; Immunopathology; Dendritic cell; Immune response; Hematology; Vaccination; Malignant hemopathy; Cellular immunity; Cell fusion; Myeloma; Prevention; Immunoglobulinopathy; Antigen presenting cell; Lymphoproliferative syndrome; Tumor cell; Humoral immunity; Cancer
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-04-277137

We have developed a tumor vaccine in which patient-derived myeloma cells are chemically fused with autologous dendritic cells (DCs) such that a broad spectrum of myeloma-associated antigens are presented in the context of DC-mediated costimulation. We have completed a phase 1 study in which patients with multiple myeloma underwent serial vaccination with the DC/multiple myeloma fusions in conjunction with granulocyte-macrophage colony-stimulating factor. DCs were generated from adherent mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-α and fused with myeloma cells obtained from marrow aspirates. Vaccine generation was successful in 17 of 18 patients. Successive cohorts were treated with 1 × 106, 2 × 106, and 4 × 106 fusion cells, respectively, with 10 patients treated at the highest dose level. Vaccination was well tolerated, without evidence of dose-limiting toxicity. Vaccination resulted in the expansion of circulating CD4 and CD8 lymphocytes reactive with autologous myeloma cells in 11 of 15 evaluable patients. Humoral responses were documented by SEREX (Serologic Analysis of Recombinant cDNA Expression Libraries) analysis. A majority of patients with advanced disease demonstrated disease stabilization, with 3 patients showing ongoing stable disease at 12, 25, and 41 months, respectively. Vaccination with DC/multiple myeloma fusions was feasible and well tolerated and resulted in antitumor immune responses and disease stabilization in a majority of patients.