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全身性给予咪喹莫特作为佐剂可提高肿瘤裂解物疫苗的免疫原性,从而诱导高度侵袭性 T 细胞淋巴瘤的排斥。

Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma.

机构信息

Centro de Estudios Farmacológicos y Botánicos-Consejo Nacional de Investigaciones Científicas y Técnicas (CEFYBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, 2155 Paraguay, Ciudad Autonoma de Buenos Aires C1121ABG, Argentina.

Centro de Estudios Farmacológicos y Botánicos-Consejo Nacional de Investigaciones Científicas y Técnicas (CEFYBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, 2155 Paraguay, Ciudad Autonoma de Buenos Aires C1121ABG, Argentina.

出版信息

Clin Immunol. 2019 Jun;203:154-161. doi: 10.1016/j.clim.2019.04.013. Epub 2019 Apr 29.

DOI:10.1016/j.clim.2019.04.013
PMID:31048012
Abstract

T-cell lymphomas include diverse malignancies. They are rare, some have low survival rates and they lack curative therapies. The aim of this work was to assess whether employing the TLR7 agonist imiquimod and the T-cell costimulatory molecule CD40 or the combination of both as adjuvants of a cell lysate vaccine could enhance the antitumor immune response using a murine T-cell lymphoma model. Immunization with LBC-lysate and imiquimod protected almost all vaccinated animals. A specific humoral and a Th1-type cellular immunity were induced in mice that rejected the lymphoma, characterized by an elevated number of CD4 + T-cells and secretion of IFN-γ, locally and systemically. In contrast, CD40 alone or in combination with imiquimod did not improve the protective response obtained with LBC-lysate and imiquimod. Systemic administration of imiquimod proved to have high potential to serve as a vaccine adjuvant for the treatment of T-cell lymphomas and was effective in this immunotherapy model.

摘要

T 细胞淋巴瘤包括多种恶性肿瘤。它们较为罕见,部分患者的生存率较低,且缺乏可治愈的疗法。本研究旨在评估 TLR7 激动剂咪喹莫特和 T 细胞共刺激分子 CD40 或两者联合作为细胞裂解物疫苗佐剂是否能增强使用鼠 T 细胞淋巴瘤模型的抗肿瘤免疫反应。用 LBC-裂解物和咪喹莫特进行免疫接种可保护几乎所有接种疫苗的动物。在拒绝淋巴瘤的小鼠中诱导了特异性体液和 Th1 型细胞免疫,其特征在于局部和全身 CD4+T 细胞数量增加和 IFN-γ的分泌。相比之下,CD40 单独或与咪喹莫特联合使用并不能提高用 LBC-裂解物和咪喹莫特获得的保护反应。全身给予咪喹莫特被证明具有作为 T 细胞淋巴瘤治疗疫苗佐剂的高潜力,并且在这种免疫治疗模型中是有效的。

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Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma.全身性给予咪喹莫特作为佐剂可提高肿瘤裂解物疫苗的免疫原性,从而诱导高度侵袭性 T 细胞淋巴瘤的排斥。
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