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首页> 外文期刊>Small >Immune Checkpoint Blockade Mediated by a Small-Molecule Nanoinhibitor Targeting the PD-1/PD-L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer
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Immune Checkpoint Blockade Mediated by a Small-Molecule Nanoinhibitor Targeting the PD-1/PD-L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer

机译：由小分子纳米烟穴介导的免疫检查点延迟靶向PD-1 / PD-L1途径的促进促进光动力疗法，以引发抗肿瘤免疫和对乳腺癌的抗致抗体作用

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摘要

Targeting programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol-Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS-202 is a small-molecule inhibitor of the PD-1/PD-L1 interaction that is developed by BMS. Transfer of BMS-202 NPs to 4T1 tumor-bearing mice results in markedly slower tumor growth to the same degree as treatment with anti-PD-L1 monoclonal antibody (α-PD-L1). Consistently, the combination of Ce6 NPs with BMS-202 NPs or α-PD-L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen-specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS-202 NPs are able to attack spreading metastatic lung tumors and offer immune-memory protection to prevent tumor relapse. These results indicate that BMS-202 NPs possess effects similar to α-PD-L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS-202 NPs.
机译：靶向编程的细胞死亡蛋白1（PD-1）/编程死亡配体1（PD-L1）免疫检查点延迟，具有单克隆抗体的抗体已经实现了抗肿瘤疗法的临床成功。然而，治疗性抗体表现出几个问题，例如有限的肿瘤渗透，免疫原性和昂贵的生产。在这里，使用再沉淀方法制备布里斯托尔 - 麦布斯氏菌纳米粒子（NPS）。 NPS具有包括被动靶向，亲水和无毒特征的优点，以及100％的药物负载率。 BMS-202是由BMS开发的PD-1 / PD-L1相互作用的小分子抑制剂。将BMS-202 NPS转移至4T1肿瘤的小鼠导致肿瘤生长显着较慢，与抗PD-L1单克隆抗体（α-PD-L1）的处理相同。始终如一地，CE6 NPS与BMS-202NPS或α-PD-L1并联的组合显示出更有效的抗肿瘤和抗体效应，伴随着增强的树突细胞成熟和抗原特异性T细胞的渗透到肿瘤中。因此，初级和远处肿瘤的抑制率达到> 90％。此外，BMS-202 NPS能够攻击扩散转移性肺肿瘤，并提供免疫记忆保护，以防止肿瘤复发。这些结果表明BMS-202 NPS具有与4T1肿瘤的治疗中的α-PD-L1类似的效果。因此，该工作揭示了用BMS-202 NPS替代免疫疗法中使用的抗体的可能性。

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  • 来源
    《Small》 |2019年第49期|共13页
  • 作者

    Rui Zhang; Zhiyan Zhu; Hongying Lv; Futian Li; Shuqing Sun; Juan Li; Chun-Sing Lee;

  • 作者单位

    Department of Chemistry City University of Hong Kong Hong Kong 999077 P. R. China;

    Tianjin Research Center of Basic Medical Science Tianjin Medical University Tianjin 300070 P. R. China;

    Chinese Academy of Medical Sciences Institute of Radiation Medicine Tianjin 300192 P. R. China;

    Chinese Academy of Medical Sciences Institute of Radiation Medicine Tianjin 300192 P. R. China;

    Department of Chemistry Tianjin University Tianjin 300072 P. R. China;

    Department of Hygienic Inspection School of Public Health Jilin University Changchun 130021 Jilin P. R. China;

    Department of Chemistry City University of Hong Kong Hong Kong 999077 P. R. China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 特种结构材料;
  • 关键词

    breast tumors; immune checkpoint blockade; PD-1/PD-L1; photodynamic therapy; small molecular inhibitors;

    机译：乳腺肿瘤;免疫检查点封闭;PD-1 / PD-L1;光动力疗法;小分子抑制剂;

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