Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.
Induction of Immune Response after Allogeneic Wilms' Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse.
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血液系统恶性肿瘤和移植后复发患者在同种异体肾母细胞瘤 1 树突状细胞疫苗接种和供体淋巴细胞输注后诱导免疫反应。
DOI：
10.1016/j.bbmt.2016.08.028
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Fry,TerryJ
中科院分区：
文献类型：
--
作者：
Shah,NiraliN;Loeb,DavidM;Khuu,Hahn;Stroncek,David;Ariyo,Tolu;Raffeld,Mark;Delbrook,Cindy;Mackall,CrystalL;Wayne,AlanS;Fry,TerryJ
恶性血液病的复发是异基因造血干细胞移植治疗失败的主要原因。供者淋巴细胞输注(DLI)治疗HCT后复发的效果有限，尤其是在急性白血病的情况下，并可能导致移植物抗宿主病(GVHD)的发展。Wilms‘s Tumor 1(WT1)基因产物是一种肿瘤相关抗原，在急性白血病和其他血液系统恶性肿瘤中表达，在正常组织中表达有限。在这项初步试验中，我们评估了WT1多肽负载供体来源的树突状细胞(DC)疫苗的安全性和可行性，该疫苗与DLI一起给予，旨在增强和指导移植物抗白血病效应。次要目标是评估免疫学和临床反应。共有5名受试者，中位年龄17岁(范围9至19岁)，在HCT后复发。疾病亚型包括急性淋巴细胞性白血病(n = 3)、急性髓系白血病(n = 1)和霍奇金淋巴瘤(n = 1)。从所有捐赠者那里成功生产疫苗是可行的。DC疫苗接种和DLI耐受性良好。1例受者发展为1级皮肤移植物抗宿主病，不需要系统治疗。最常见的不良事件包括疫苗注射时的1级可逆性疼痛和瘙痒，以及迟发型超敏反应(DTH)皮肤测试部位。没有与研究相关的3级或更高级别的不良事件。免疫反应包括3例受体的ELISpot反应和2例WT1多肽鸡尾酒的DTH阳性反应。我们的研究提供了将肿瘤特异性疫苗疗法应用于异基因环境的首次尝试。初步结果表明，同种异体血细胞移植后DC疫苗接种是安全可行的，提示这种方法可以用来增强再繁殖的异基因供者免疫系统对WT1的敏感性。未来的方向可能包括在移植后早期测试预防复发的疫苗接种策略。
Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues. In this pilot trial, we assessed safety and feasibility of a WT1 peptide–loaded donor-derived dendritic cell (DC) vaccine given with DLI designed to enhance and direct the graft-versus-leukemia effect. Secondary objectives were to evaluate immunologic and clinical responses. A total of 5 subjects, median age 17 years (range, 9 to 19 years), with post-HCT relapse were enrolled. Disease subtypes included acute lymphoblastic leukemia (n = 3), acute myelogenous leukemia (n = 1), and Hodgkin lymphoma (n = 1). Successful vaccine production was feasible from all donors. DC vaccination and DLI were well tolerated. One recipient developed grade 1 skin GVHD not requiring systemic therapy. The most common adverse events included grade 1 reversible pain and pruritus at the vaccine injection and delayed-type hypersensitivity (DTH) skin testing sites. There were no grade 3 or higher adverse events related to the research. Immune responses consisted of ELISpot response in 3 recipients and positive DTH tests to WT1 peptide cocktail in 2 subjects. Our study provides 1 of the first attempts to apply tumor-specific vaccine therapy to the allogeneic setting. Preliminary results show the DC-based vaccination is safe and feasible after allogeneic HCT, with a suggestion that this approach can be used to sensitize the repopulated allogeneic-donor immune system to WT1. Future directions may include testing of vaccination strategies in the early post-transplantation setting for relapse prevention.
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影响因子：
11.2
作者：
D. Loeb;E. Evron;C. B. Patel;Prem M. Sharma;B. Niranjan;L. Buluwela;S. Weitzman;Dorian Korz;S. Sukumar
通讯作者：
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20.3
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20.3
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影响因子：
15.9
作者：
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通讯作者：
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