A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS
A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS
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DOI：
10.1182/blood-2009-02-202598
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发表时间：
2009-06-25
期刊：
影响因子：
20.3
通讯作者：
Scheibenbogen, Carmen
中科院分区：
文献类型：
--
作者：
Keilholz, Ulrich;Letsch, Anne;Scheibenbogen, Carmen
本研究调查了Wilms肿瘤基因产物1（WT 1）-肽疫苗在表达WT 1的急性髓性白血病（AML）和骨髓增生异常综合征（MDS）患者中的免疫原性，这些患者没有治愈性治疗选择。疫苗接种包括第1 - 4天皮下注射粒细胞-巨噬细胞集落刺激因子，第3天注射WT 1.126 -134肽和1 mg钥孔血蓝蛋白。最初的9名患者每两周接种4次疫苗，然后每月接种一次，随后的10名患者每两周接种一次疫苗。17名AML患者和2名难治性贫血伴原始细胞过多患者接受了中位数为11次的疫苗接种。治疗耐受性良好。AML患者的客观缓解为10例疾病稳定（SD），包括4例原始细胞减少超过50%的SD和2例血液学改善。另外4例患者在初始进展后有临床获益，包括1例完全缓解和3例SD。在35%的患者中，WT 1 mRNA水平较基线降低至少3倍。在18名患者中的8名中，血液中的WT 1-四聚体（+）T细胞增加，在17名患者中的8名中，骨髓中的中位频率在基线时为0.18%，在第18周为0.41%。这项WT 1疫苗接种研究为AML患者提供了潜在临床疗效的免疫学、分子学和初步证据，从而促进了进一步的研究。（血。2009; 113：6541-6548）
This study investigated the immunogenicity of Wilms tumor gene product 1 (WT1)-peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients without curative treatment option. Vaccination consisted of granulocyte-macrophage colony-stimulating factor subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly, then monthly, and the subsequent 10 patients received continual biweekly vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs with more than 50% blast reduction and 2 with hematologic improvement. An additional 4 patients had clinical benefit after initial progression, including 1 complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer(+) T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations. (Blood. 2009; 113: 6541-6548)