WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.
WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.
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DOI：
10.1002/ajh.24014
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发表时间：
2015-07
影响因子：
12.8
通讯作者：
Pinilla-Ibarz J
中科院分区：
文献类型：
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作者：
Brayer J;Lancet JE;Powers J;List A;Balducci L;Komrokji R;Pinilla-Ibarz J
肽疫苗能够引发靶向肿瘤相关抗原的免疫应答，例如通常在骨髓恶性肿瘤中过表达的Wilms肿瘤1（WT 1）抗原。在这里，我们评估了多价WT1肽疫苗的安全性、耐受性和免疫原性。WT1阳性急性髓性白血病（AML）患者在第一次（CR1）或第二次（CR2）缓解期或在至少一线既往治疗后患有高危骨髓增生异常综合征（MDS），在接种疫苗前使用源自WT1蛋白的肽混合物接种疫苗，并注射沙格司亭以增强免疫原性。每两周接种六次疫苗，然后每月接种一次，直到患者接受12次疫苗接种或显示疾病复发或进展。通过无进展生存期和总生存期评价疗效。通过迟发型超敏反应试验和T细胞IFNγ ELISPOT在规定的时间间隔评价免疫应答。在16名至少接受过一次疫苗接种的患者中，10名完成了计划的六次疫苗接种，6名继续进行最多六次额外的每月疫苗接种。疫苗接种耐受性良好，没有患者因毒性而停药。2例高危MDS患者中有1例输血依赖性长期下降。14例AML患者中有2例显示无复发生存期>1年。两例患者在接种疫苗时均处于CR2，其缓解持续时间超过其首次缓解持续时间，表明潜在获益。我们的WT1疫苗耐受性良好。我们在一些患者中观察到的临床益处表明参与了保护性免疫反应，表明需要进一步试验。
Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms’ Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials.