title: Successful cross-presentation of allogeneic myeloma cells by autologous alpha-type 1-polarized dendritic cells as an effective tumor antigen in myeloma patients with matched monoclonal immunoglobulins.
abstract: For wide application of a dendritic cell (DC) vaccination in myeloma patients, easily available tumor antigens should be developed. We investigated the feasibility of cellular immunotherapy using autologous alpha-type 1-polarized dendritic cells (αDC1s) loaded with apoptotic allogeneic myeloma cells, which could generate myeloma-specific cytotoxic T lymphocytes (CTLs) against autologous myeloma cells in myeloma patients. Monocyte-derived DCs were matured by adding the αDC1-polarizing cocktail (TNFα/IL-1β/IFN-α/IFN-γ/poly-I:C) and loaded with apoptotic allogeneic CD138(+) myeloma cells from other patients with matched monoclonal immunoglobulins as a tumor antigen. There were no differences in the phenotypic expression between αDC1s loaded with apoptotic autologous and allogeneic myeloma cells. Autologous αDC1s effectively took up apoptotic allogeneic myeloma cells from other patients with matched subtype. Myeloma-specific CTLs against autologous target cells were successfully induced by αDC1s loaded with allogeneic tumor antigen. The cross-presentation of apoptotic allogeneic myeloma cells to αDC1s could generate CTL responses between myeloma patients with individual matched monoclonal immunoglobulins. There was no difference in CTL responses between αDC1s loaded with autologous tumor antigen and allogeneic tumor antigen against targeting patient's myeloma cells. Our data indicate that autologous DCs loaded with allogeneic myeloma cells with matched immunoglobulin can generate potent myeloma-specific CTL responses against autologous myeloma cells and can be a highly feasible and effective method for cellular immunotherapy in myeloma patients.
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 160 Ilsimri, Hwasun, Jeollanamdo, 519-809, South Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.forename: Youn-Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Cheol Yi
authors.initials: CY
authors.lastname: Hong
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Thanh-Nhan
authors.initials: TN
authors.lastname: Nguyen-Pham
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Bae
authors.forename: Jae-Sook
authors.initials: JS
authors.lastname: Ahn
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014182:Transplantation, Autologous / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines