Wilms Tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma
Wilms Tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma
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DOI：
10.1532/ijh97.07007
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发表时间：
2007-12
影响因子：
2.1
通讯作者：
A. Tsuboi;Y. Oka;H. Nakajima;Y. Fukuda;O. Elisseeva;S. Yoshihara;N. Hosen;A. Ogata;K. Kito;F. Fujiki;S. Nishida;T. Shirakata;S. Ohno;M. Yasukawa;Y. Oji;M. Kawakami;S. Morita;J. Sakamoto;K. Udaka;I. Kawase;H. Sugiyama
中科院分区：
文献类型：
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作者：
A. Tsuboi;Y. Oka;H. Nakajima;Y. Fukuda;O. Elisseeva;S. Yoshihara;N. Hosen;A. Ogata;K. Kito;F. Fujiki;S. Nishida;T. Shirakata;S. Ohno;M. Yasukawa;Y. Oji;M. Kawakami;S. Morita;J. Sakamoto;K. Udaka;I. Kawase;H. Sugiyama
Wilms肿瘤基因的产物WT 1是一种通用的肿瘤抗原。我们对多发性骨髓瘤（MM）患者进行了基于WT 1肽的免疫治疗。该患者是一名57岁女性，患有化疗耐药MM（Bence Jones к型）。该患者每周皮内注射用Montanide伊萨51佐剂乳化的HLA-A*2402限制性9聚体WT 1肽12周，并根据欧洲血液和骨髓移植组标准实现最小应答，而没有经历全身不良反应。WT 1疫苗接种后，骨髓（BM）中骨髓瘤细胞的比例从85%降至25%，尿液中M蛋白的量从3.6 g/天降至0.6 g/天。此外，骨密度图显示接种疫苗后有所改善。对于免疫学参数，CD 8 + T细胞中的WT 1四聚体阳性细胞的频率高于健康供体，但在第4周和第8周时暂时降低，但在第12周时增加，而WT 1四聚体阳性T细胞中的WT 1肽应答性CD 107 a/B+细胞的频率在接种后从27.0%增加到38.6%。WT 1疫苗接种后，在BM中WT 1四聚体阳性T细胞中CXCR 4+细胞的频率增加，其中基质细胞表达CXCR 4的配体，基质衍生因子1（SDF-1），但在外周血（PB）中减少，这意味着WT 1特异性细胞毒性T淋巴细胞已从PB迁移到BM（肿瘤部位）。
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.