Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma.
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.
Tsuboi
Akihiro
A
Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita City, Osaka, Japan.
Oka
Yoshihiro
Y
Nakajima
Hiroko
H
Fukuda
Yoko
Y
Elisseeva
Olga A
OA
Yoshihara
Satoshi
S
Hosen
Naoki
N
Ogata
Atsushi
A
Kito
Katsuyuki
K
Fujiki
Fumihiro
F
Nishida
Sumiyuki
S
Shirakata
Toshiaki
T
Ohno
Satoshi
S
Yasukawa
Masaki
M
Oji
Yusuke
Y
Kawakami
Manabu
M
Morita
Satoshi
S
Sakamoto
Junichi
J
Udaka
Keiko
K
Kawase
Ichiro
I
Sugiyama
Haruo
H
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*
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