B052:腺病毒介导的全长抗体nivolumab对黑色素瘤的免疫治疗

Xuchen Wang
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摘要

Nivolumab是一种全人源IgG4免疫检查点抑制剂抗体,可将PD-1结合在活化的免疫细胞上,破坏PD-1与PD-L1和PD-L2配体的相互作用,从而减弱抑制信号并增强宿主抗肿瘤反应。2014年,nivolumab获得FDA批准,已被用于治疗各种类型的癌症,如黑色素瘤、非小细胞肺癌、肾细胞癌和经典霍奇金淋巴瘤。然而,由于纳武单抗价格高,治疗周期长,许多患者无法负担和接受足够的治疗。在这里,我们通过将nivolumab抗体全长基因克隆到两种血清型腺病毒载体(AdHu5-Nivo和AdC68-Nivo)中,生成了一种新的,更便宜的用于癌症免疫治疗的nivolumab形式。基于人血清5型(AdHu5)的Ad载体已被大量研究证明是安全有效的。与AdHu5相比,黑猩猩Ad在人体内的血清阳性率低得多,这使它们成为了很好的替代Ad基因载体。到目前为止,我们已经通过Western blot和夹心ELISA在体外检测到nivolumab的高表达。体内研究表明,单剂量AdHu5-Nivo或AdC68-Nivo可诱导持续的nivolumab表达。这两种单克隆抗体的生物活性与市售单克隆抗体相似。接下来,我们将在细胞水平和黑色素瘤移植动物模型上验证它们的抗肿瘤作用。引用格式:王旭晨。腺病毒介导的全长抗体nivolumab对黑色素瘤的免疫治疗[摘要]。第四届CRI-CIMT-EATI-AACR国际癌症免疫治疗会议:将科学转化为生存;2018年9月30日至10月3日;纽约,纽约。费城(PA): AACR;癌症免疫学杂志,2019;7(2增刊):摘要nr B052。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abstract B052: Immunotherapy for melanoma by adenovirus-mediated full-length antibody, nivolumab
Nivolumab, a fully human, IgG4 immune checkpoint inhibitor antibody, binds PD-1 on activated immune cells to disrupt PD-1 interaction with PD-L1 and PD-L2 ligands, thereby attenuating inhibitory signals and augmenting the host antitumour response. In 2014, nivolumab was approved by FDA and has been used to treat various types of cancer such as melanoma, non-small cell lung cancer, renal cell carcinoma, and classic Hodgkin9s lymphoma. However, due to the high price of nivolumab and the long cycle of treatment, many patients cannot afford and receive adequate treatment. Here, we generated a new, cheaper form of nivolumab for cancer immunotherapy, by cloning the full-length nivolumab antibody gene into two serotypes of adenovirus vectors, termed as AdHu5-Nivo and AdC68-Nivo. Ad vectors based on human serotype 5 (AdHu5) have been proved in a lot of previous studies to be safe and efficient. Compared with AdHu5, chimpanzee Ads exhibit much lower seroprevalence in human beings, which made them great alternative Ad gene vector. Until now, we have detected a high expression of nivolumab in vitro by Western blot and sandwich ELISA. In vivo studies showed that a single dose of AdHu5-Nivo or AdC68-Nivo can induce sustained nivolumab expression. The biologic activities of the two mAbs are analogous compared with commercial monoclonal antibody. To follow up we will verify their antitumor effects on both cellular level and melanoma transplant animal models. Citation Format: Xuchen Wang. Immunotherapy for melanoma by adenovirus-mediated full-length antibody, nivolumab [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B052.
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