A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances antigen-specific T-cell responses.
A fully human IgG1 anti-PD-L1 MAb in an in vitro assay enhances antigen-specific T-cell responses.
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DOI：
10.1038/cti.2016.27
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发表时间：
2016-05
影响因子：
5.8
通讯作者：
Schlom J
中科院分区：
文献类型：
--
作者：
Grenga I;Donahue RN;Lepone LM;Richards J;Schlom J
干扰检查点分子的单克隆抗体（mab）正在被研究用于治疗传染病和癌症，目的是增强受损免疫系统的功能。Avelumab （MSB0010718C）是一种针对程序性死亡配体1 （PD-L1）的全人IgG1单抗，其介导抗体依赖性细胞介导的细胞毒性的能力与其他检查点阻断抗体不同。这些研究是为了确定avelumab是否可以在体外检测中增强抗原特异性免疫反应的检测。用编码巨细胞病毒、爱泼斯坦-巴尔病毒、流感和破伤风毒素的肽库或编码人类白细胞抗原的阴性肽对照，体外刺激17例健康供体外周血单个核细胞。这些研究首次表明，将avelumab添加到抗原特异性IVS试验中(a)增加了活化抗原特异性CD8+ T淋巴细胞的频率，并且比市售的pd - l1阻断抗体更大程度上这样做，(b)减少了CD4+ T细胞的增殖，(c)诱导Th2到Th1细胞因子的产生转换。此外，avelumab诱导的CD8+ t细胞活化的增强与CD4+ t细胞增殖的减少之间存在负相关。这些发现为在体外检测中使用avelumab抗pd - l1来监测患者对免疫疗法的免疫反应提供了理论依据。
Monoclonal antibodies (MAbs) that interfere with checkpoint molecules are being investigated for the treatment of infectious diseases and cancer, with the aim of enhancing the function of an impaired immune system. Avelumab (MSB0010718C) is a fully human IgG1 MAb targeting programmed death-ligand 1 (PD-L1), which differs from other checkpoint-blocking antibodies in its ability to mediate antibody-dependent cell-mediated cytotoxicity. These studies were conducted to define whether avelumab could enhance the detection of antigen-specific immune response in in vitro assays. Peripheral blood mononuclear cells from 17 healthy donors were stimulated in vitro, with and without avelumab, with peptide pools encoding for cytomegalovirus, Epstein–Barr virus, influenza and tetanus toxin or the negative peptide control encoding for human leukocyte antigen. These studies show for the first time that the addition of avelumab to an antigen-specific IVS assay (a) increased the frequency of activated antigen-specific CD8+ T lymphocytes, and did so to a greater extent than that seen with commercially available PD-L1-blocking antibodies, (b) reduced CD4+ T-cell proliferation and (c) induced a switch in the production of Th2 to Th1 cytokines. Moreover, there was an inverse correlation between the enhancement of CD8+ T-cell activation and reduction in CD4+ T-cell proliferation induced by avelumab. These findings provide the rationale for the use of avelumab anti-PD-L1 in in vitro assays to monitor patient immune responses to immunotherapies.