PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses
PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses
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DOI：
10.1016/j.cellimm.2014.01.003
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发表时间：
2014-02-01
影响因子：
4.3
通讯作者：
Ye, Yunbin
中科院分区：
文献类型：
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作者：
Chen, Mingshui;Ouyang, Haichao;Ye, Yunbin
OX 40（CD 134）是主要在活化的T细胞上表达的肿瘤坏死因子（TNF）受体，并且一旦接合就传递有效的共刺激信号。激动性抗0X 40单克隆抗体（mAb）增强肿瘤免疫应答，从而在小鼠肿瘤模型中产生治疗效果。然而，当在I期临床试验中进行测试时，它在癌症患者中没有显示出客观的临床活性。在这项研究中，我们研究了纳米颗粒（NP）介导的抗OX 40单克隆抗体有效诱导细胞毒性T淋巴细胞（CTL）反应的可行性。采用复乳法制备了载抗OX 40单克隆抗体的可生物降解聚（间丙交酯-共-乙交酯）纳米粒（anti-OX 40-PLGA-NP），其平均粒径为86 nm，载药率为25%。我们发现抗OX 40-PLGA-NP比游离抗OX 40 mAb更强地诱导CTL增殖和肿瘤抗原特异性细胞毒性以及细胞因子产生。这些结果表明，基于PLGA的纳米颗粒制剂可以提供用于癌症免疫治疗的抗0X 40 mAb的有效递送系统。(C)2014爱思唯尔公司All rights reserved.
OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed mainly on activated T cells and transmits a potent costimulatory signal once engaged. Agonistic anti-OX40 monoclonal antibody (mAb) enhances tumor immune response leading to therapeutic effects in mouse tumor models. However, when tested in phase I clinical trials it did not show objective clinical activity in cancer patients. In this study, we examined the feasibility of nanoparticle (NP)-mediated delivery of anti-OX40 mAb to efficiently induce cytotoxic T lymphocyte (CTL) responses. The biodegradable poly(m-lactide-co-glycolide) nanoparticle (PLGA-NP) carrying anti-OX40 mAb, anti-OX40-PLGA-NP, was prepared by double emulsion method and showed an average diameter of 86 nm with a loading efficiency of 25%. We found that anti-OX40-PLGA-NP induced CTL proliferation and tumor antigen-specific cytotoxicity as well as cytokine production more strongly than free anti-OX40 mAb. These results suggest that PLGA-based nanoparticle formulation may provide efficient delivery system of anti-OX40 mAb for cancer immunotherapy. (C) 2014 Elsevier Inc. All rights reserved.