Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma

• Published in: British journal of haematology Vol. 125; no. 3; pp. 343 - 352
• Main Authors: Raje, Noopur, Hideshima, Teru, Davies, Faith E., Chauhan, Dharminder, Treon, Steven P., Young, Gloria, Tai, Yu‐Tzu, Avigan, David, Gong, Jianlin, Schlossman, Robert L., Richardson, Paul, Kufe, Donald W., Anderson, Kenneth C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: Antigen Presentation - immunology; autologous; Biological and medical sciences; Cancer Vaccines - immunology; Cell Fusion - methods; cytotoxicity; Cytotoxicity, Immunologic; dendritic cells; Dendritic Cells - immunology; Hematologic and hematopoietic diseases; Hematology; Humans; Immunity, Cellular; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunophenotyping; immunotherapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; Medical sciences; Microscopy, Fluorescence; Multiple Myeloma - immunology; Multiple Myeloma - pathology; T-Lymphocytes - immunology; Tumor Cells, Cultured; vaccines; Immunopathology; Dendritic cell; Hematology; vaccines; Vaccination; Cytotoxicity; Malignant hemopathy; Vaccine; Cell fusion; Myeloma; Prevention; Immunoprophylaxis; Treatment; dendritic cells; Immunoglobulinopathy; Antigen presenting cell; Lymphoproliferative syndrome; Immunotherapy; autologous; Tumor
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.04929.x

Summary Multiple myeloma (MM) cells express certain tumour‐associated antigens (TAAs) that could serve as targets for active‐specific immunotherapy. The aim of the present study was to test the MM/dendritic cell (DC) fusion as a vaccination strategy. We fused MM cells with DC to generate fusion cells (FCs) and tested their antigen presenting cell (APC) function in mixed lymphocyte reactions and cytotoxicity assays. First, the HS Sultan and SK0‐007 HAT sensitive human MM cell lines and DCs generated from peripheral blood of normal donors were fused in the presence of 50% polyethylene glycol to form FCs. Next, tumour cells freshly isolated from patients were similarly fused with autologous DCs to generate FCs. The FCs demonstrated a biphenotypic profile, confirmed both by flow‐cytometry and dual immunofluorescence microscopy. These FCs induced MM‐specific cytotoxicity. FCs, but not MM cells or DCs alone, were potent stimulators of autologous patient T cells. More importantly, FC‐primed autologous peripheral blood mononuclear cells demonstrated major histocompatibility complex‐restricted MM‐specific cytolysis. These studies therefore demonstrated that MM/DC FC can trigger an autologous immune response to MM cells and formed the framework for a clinical trial currently underway.