title: Immunogenicity of dendritic cells pulsed with MAGE3, Survivin and B-cell maturation antigen mRNA for vaccination of multiple myeloma patients.
abstract: The introduction of autologous stem cell transplantation (SCT) and novel drugs has improved overall survival in multiple myeloma (MM) patients. However, minimal residual disease (MRD) remains and most patients eventually relapse. Myeloma plasma cells express tumor-associated antigens (TAA), which are interesting targets for immunotherapy. In this phase 1 study, we investigated the safety and immunological effects of TAA-mRNA-loaded dendritic cell (DC) vaccination for treatment for MRD in MM after SCT. Mature monocyte-derived DCs were pulsed with keyhole limpet hemocyanin (KLH) and electroporated with MAGE3, Survivin or B-cell maturation antigen (BCMA) mRNA. Twelve patients were vaccinated three times with intravenous (5-22 × 10(6) DCs) and intradermal vaccines (4-11 × 10(6) DCs), at biweekly intervals. Immunological responses were monitored in blood and delayed-type hypersensitivity (DTH) biopsies. All patients developed strong anti-KLH T-cell responses, but not KLH antibodies. In 2 patients, vaccine-specific T cells were detected in DTH biopsies. In one patient, we found MAGE3-specific CD4(+) and CD8(+) T cells, and CD3(+) T cells reactive against BCMA and Survivin. In the other patient, we detected low numbers of MAGE3 and BCMA-reactive CD8(+) T cells. Vaccination was well tolerated with limited toxicity. These findings illustrate that TAA-mRNA-electroporated mature DCs are capable of inducing TAA-T-cell responses in MM patients after SCT.
authors.affiliation: Laboratory of Hematology, Department of Laboratory Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Willemijn
authors.initials: W
authors.lastname: Hobo
authors.forename: Leonie
authors.initials: L
authors.lastname: Strobbe
authors.forename: Frans
authors.initials: F
authors.lastname: Maas
authors.forename: Hanny
authors.initials: H
authors.lastname: Fredrix
authors.forename: Annelies
authors.initials: A
authors.lastname: Greupink-Draaisma
authors.forename: Ben
authors.initials: B
authors.lastname: Esendam
authors.forename: Theo
authors.initials: T
authors.lastname: de Witte
authors.forename: Frank
authors.initials: F
authors.lastname: Preijers
authors.forename: Henriëtte
authors.initials: H
authors.lastname: Levenga
authors.forename: Bas
authors.initials: B
authors.lastname: van Rees
authors.forename: Reinier
authors.initials: R
authors.lastname: Raymakers
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Schaap
authors.forename: Harry
authors.initials: H
authors.lastname: Dolstra
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D053301:B-Cell Maturation Antigen / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009101:Multiple Myeloma / Q000276:immunology* / Q000601:surgery / Q000628:therapy; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual / Q000276:immunology / Q000601:surgery / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D033581:Stem Cell Transplantation / Q000379:methods; D000077022:Survivin; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D053301:B-Cell Maturation Antigen; C107489:BIRC5 protein, human; D017252:CD3 Complex; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin