title: Preclinical development of hybrid cell vaccines for multiple myeloma.
abstract: Immunotherapy may provide alternative or supplementary treatment of multiple myeloma (MM). We propose that hybrid cells, formed by fusing professional antigen-presenting cells with malignant plasma cells, would induce immune responses capable of mediating tumour regression. The human B-lymphoblastoid cell line, HMy2, was fused in vitro with CD138+ bead-separated myeloma plasma cells from five patients with MM. The hybrid cell lines generated in these studies grew stably in tissue culture, and maintained their phenotypic and functional characteristics, providing self-renewing cell lines with potential for therapeutic vaccination. The hybrid cells stimulated allogeneic and autologous T-cell proliferative responses in vitro to a considerably greater degree than their respective parent myeloma plasma cells, and directly activated both CD4+ and CD8+ T-cell responses. The enhanced T-cell stimulation correlated with expression of CD80 on the hybrid cells, and was inhibited by CTLA4-Ig fusion protein. The hybrid cell lines expressed several tumour-associated antigens known to be expressed in myeloma. These data show that self-replicating cell lines with enhanced immunostimulatory properties and potential for therapeutic vaccination can be generated by in vitro fusion of ex vivo myeloma cells and B-lymphoblastoid cell lines.
authors.affiliation: Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, UK.
authors.forename: Renata
authors.initials: R
authors.lastname: Walewska
authors.forename: Iryna
authors.initials: I
authors.lastname: Teobald
authors.forename: Debbie
authors.initials: D
authors.lastname: Dunnion
authors.forename: Hind
authors.initials: H
authors.lastname: Abdulmajed
authors.forename: Micheala
authors.initials: M
authors.lastname: Aldred
authors.forename: Jean
authors.initials: J
authors.lastname: Sadler
authors.forename: Claire
authors.initials: C
authors.lastname: Chapman
authors.forename: Michael
authors.initials: M
authors.lastname: Browning
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D020732:Cytogenetic Analysis; D005434:Flow Cytometry; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology*; D007159:Immunologic Tests; D016130:Immunophenotyping; D018895:Microsatellite Repeats; D009101:Multiple Myeloma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines