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Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma.
- Source :
-
International journal of hematology [Int J Hematol] 2007 Dec; Vol. 86 (5), pp. 414-7. - Publication Year :
- 2007
-
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.
- Subjects :
- Bone Marrow immunology
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines immunology
Chemokine CXCL12 immunology
Chemokine CXCL12 metabolism
Drug Resistance, Neoplasm drug effects
Female
HLA-A Antigens immunology
HLA-A24 Antigen
Humans
Lymphocyte Count
Lysosomal-Associated Membrane Protein 1 immunology
Lysosomal-Associated Membrane Protein 1 metabolism
Lysosomal-Associated Membrane Protein 2 immunology
Lysosomal-Associated Membrane Protein 2 metabolism
Mannitol therapeutic use
Middle Aged
Multiple Myeloma blood
Multiple Myeloma immunology
Multiple Myeloma urine
Myeloma Proteins immunology
Myeloma Proteins urine
Radionuclide Imaging
Receptors, CXCR4 immunology
Receptors, CXCR4 metabolism
Remission Induction
Time Factors
WT1 Proteins immunology
Cancer Vaccines therapeutic use
Drug Resistance, Neoplasm immunology
Mannitol analogs & derivatives
Multiple Myeloma therapy
Oleic Acids therapeutic use
Vaccination
WT1 Proteins therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0925-5710
- Volume :
- 86
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 18192109
- Full Text :
- https://doi.org/10.1532/IJH97.07007