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由 OKT3 杂交瘤释放的纳米囊泡表达完全活性的抗体。

Nanovesicles released by OKT3 hybridoma express fully active antibodies.

机构信息

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.

出版信息

J Enzyme Inhib Med Chem. 2021 Dec;36(1):175-182. doi: 10.1080/14756366.2020.1852401.

Abstract

Recent findings have shown that nanovesicles preparations from either primary immune cells culture supernatants or plasma contain immunoglobulins, suggesting that a natural way of antibody production may be through exosome release. To verify this hypothesis, we used the OKT3 hybridoma clone, which produces a murine IgG2a monoclonal antibody used to reduce rejection in patients undergoing organ transplantation. We showed exosome-associated immunoglobulins in hybridoma supernatants, by Western blot, nanoscale flow cytometry and immunocapture-based ELISA. The OKT3-exo was also being able to trigger cytokines production in both CD4 and CD8 T cells. These results show that nanovesicles contain immunoglobulin and could be used for immunotherapy. These data could lead to a new approach to improve the effectiveness of therapeutic antibodies by exploiting their natural property to be expressed on nanovesicle membrane, that probably render them more stable and as a consequence more capable to interact with their specific ligand in the best way.

摘要

最近的研究结果表明,源自原代免疫细胞培养上清液或血浆的纳米囊泡制剂中含有免疫球蛋白,这表明抗体的产生可能是通过外泌体的释放来实现的。为了验证这一假设,我们使用了 OKT3 杂交瘤克隆,该克隆产生一种用于降低器官移植患者排斥反应的鼠源性 IgG2a 单克隆抗体。我们通过 Western blot、纳米流式细胞术和基于免疫捕获的 ELISA 显示了杂交瘤上清液中的外泌体相关免疫球蛋白。OKT3-exo 还能够触发 CD4 和 CD8 T 细胞中细胞因子的产生。这些结果表明纳米囊泡含有免疫球蛋白,可用于免疫治疗。这些数据可能为通过利用治疗性抗体的天然特性将其表达在纳米囊泡膜上来提高其有效性提供一种新方法,这可能使它们更稳定,因此更能够以最佳方式与其特异性配体相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d8f/7801098/ec0dcb8f9c13/IENZ_A_1852401_F0001_B.jpg

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