International Journal of Hematology

DOI: 10.1007/BF02983998 Pages: 414-417

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

1. Osaka University Graduate School of Medicine, Department of Cancer Immunotherapy

2. Osaka University Graduate School of Medicine, Department of Respiratory Medicine, Allergy and Rheumatic Diseases

3. Osaka University Graduate School of Medicine, Department of Functional Diagnostic Science

4. Shiga University of Medical Science, Department of Hematology

5. Ehime University School of Medicine, The First Department of Internal Medicine

6. Kyoto University Graduate School of Medicine, Department of Epidemiology and Health Care Research

7. Kochi Medical School, Department of Immunology

Correspondence to:
Haruo Sugiyama
Tel: 81-6-6879-2593
Fax: 81-6-6879-2593
Email: sugiyama@sahs.med.osaka-u.ac.jp

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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 ะบ 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.

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