Wilms Tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma

  • Akihiro Tsuboi
  • Yoshihiro Oka
  • Hiroko Nakajima
  • Yoko Fukuda
  • Olga A. Elisseeva
  • Satoshi Yoshihara
  • Naoki Hosen
  • Atsushi Ogata
  • Katsuyuki Kito
  • Fumihiro Fujiki
  • Sumiyuki Nishida
  • Toshiaki Shirakata
  • Satoshi Ohno
  • Masaki Yasukawa
  • Yusuke Oji
  • Manabu Kawakami
  • Satoshi Morita
  • Junichi Sakamoto
  • Keiko Udaka
  • Ichiro Kawase
  • Haruo Sugiyama
Case Report

DOI: 10.1007/BF02983998

Cite this article as:
Tsuboi, A., Oka, Y., Nakajima, H. et al. Int J Hematol (2007) 86: 414. doi:10.1007/BF02983998

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 к 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.

Key words

Wilms tumor gene WT1 Multiple myeloma Immunotherapy Cancer vaccine 

Copyright information

© The Japanese Society of Hematology 2007

Authors and Affiliations

  • Akihiro Tsuboi
    • 1
  • Yoshihiro Oka
    • 2
  • Hiroko Nakajima
    • 3
  • Yoko Fukuda
    • 3
  • Olga A. Elisseeva
    • 3
  • Satoshi Yoshihara
    • 2
  • Naoki Hosen
    • 3
  • Atsushi Ogata
    • 2
  • Katsuyuki Kito
    • 4
  • Fumihiro Fujiki
    • 3
  • Sumiyuki Nishida
    • 3
  • Toshiaki Shirakata
    • 3
  • Satoshi Ohno
    • 1
  • Masaki Yasukawa
    • 5
  • Yusuke Oji
    • 3
  • Manabu Kawakami
    • 1
  • Satoshi Morita
    • 6
  • Junichi Sakamoto
    • 6
  • Keiko Udaka
    • 7
  • Ichiro Kawase
    • 2
  • Haruo Sugiyama
    • 3
  1. 1.Department of Cancer ImmunotherapyOsaka University Graduate School of MedicineOsakaJapan
  2. 2.Department of Respiratory Medicine, Allergy and Rheumatic DiseasesOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of Functional Diagnostic ScienceOsaka University Graduate School of MedicineSuita City, OsakaJapan
  4. 4.Department of HematologyShiga University of Medical ScienceShigaJapan
  5. 5.The First Department of Internal MedicineEhime University School of MedicineEhimeJapan
  6. 6.Department of Epidemiology and Health Care ResearchKyoto University Graduate School of MedicineKyotoJapan
  7. 7.Department of ImmunologyKochi Medical SchoolKochiJapan