title: Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma.
abstract: The product of the Wilms tumor gene, WT1, is a universal tumor antigen. We performed WT1 peptide-based immunotherapy for a patient with multiple myeloma (MM). This patient was a 57-year-old woman with chemotherapy-resistant MM (Bence Jones kappa type). The patient received weekly intradermal injections of an HLA-A*2402-restricted 9-mer WT1 peptide emulsified with Montanide ISA 51 adjuvant for 12 weeks and achieved a minimal response according to European Group for Blood and Marrow Transplantation criteria without experiencing systemic adverse effects. The proportion of myeloma cells in the bone marrow (BM) decreased from 85% to 25%, and the amount of M protein in the urine decreased from 3.6 to 0.6 g/day after WT1 vaccination. Furthermore, a bone scintigram showed an improvement after the vaccination. As for immunologic parameters, the frequency of WT1 tetramer-positive cells among CD8+ T-cells, which was higher than in healthy donors, temporarily decreased at weeks 4 and 8 but increased at week 12, whereas the frequency of WT1 peptide-responding CD107a/b+ cells among WT1 tetramer-positive T-cells increased from 27.0% to 38.6% after the vaccination. After WT1 vaccination, the frequency of CXCR4+ cells among WT1 tetramer-positive T-cells increased in the BM, where stromal cells expressed the ligand for CXCR4, stromal-derived factor 1 (SDF-1), but decreased in the peripheral blood (PB), implying that WT1-specific cytotoxic T-lymphocytes had migrated from the PB to the BM, a tumor site.
authors.affiliation: Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita City, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Olga A
authors.initials: OA
authors.lastname: Elisseeva
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogata
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kito
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujiki
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohno
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Udaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D001853:Bone Marrow / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D018655:Lymphocyte Count; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000276:immunology / Q000378:metabolism; D008353:Mannitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy* / Q000652:urine; D009194:Myeloma Proteins / Q000276:immunology / Q000652:urine; D009829:Oleic Acids / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D012074:Remission Induction; D013997:Time Factors; D014611:Vaccination; D025721:WT1 Proteins / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C515255:CXCL12 protein, human; D019496:Cancer Vaccines; D054377:Chemokine CXCL12; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D009194:Myeloma Proteins; D009829:Oleic Acids; D019718:Receptors, CXCR4; D025721:WT1 Proteins; C477385:montanide ISA 51; C085016:multiple myeloma M-proteins; D008353:Mannitol