Camrelizumab：肝细胞癌的研究药物

StephenW

Camrelizumab：肝细胞癌的研究药物
徐斌
& 孙慧川
2021 年 11 月 22 日收到，2021 年 12 月 19 日接受，在线发布已接受的作者版本：2021 年 12 月 23 日

    下载引文 https://doi.org/10.1080/13543784.2022.2022121 CrossMark 标志 CrossMark

接受的作者版本
抽象的
介绍

：虽然许多方法已用于治疗肝细胞癌 (HCC)，但临床益处有限，尤其是对于晚期 HCC。然而，最近使用 PD-1/PD-L1 抑制剂单药治疗及其与其他疗法的联合治疗已显示出显着的效果。 Camrelizumab 是一种选择性、人源化、高亲和力的 IgG4 PD-1 单克隆抗体，已被中国国家药品监督管理局批准用于晚期 HCC 患者的二线治疗。
覆盖区域

：本文介绍了晚期 HCC 的抗 PD-1/PD-L1 免疫疗法，并就卡瑞珠单抗治疗晚期 HCC 的药理学、安全性和有效性进行了讨论。它还考虑了在这种情况下卡瑞珠单抗的未来研究方向。
专家意见

：camrelizumab 的 PD-1 结合表位与其他 PD-1 抑制剂不同。 camrelizumab抑制PD-1与PD-L1结合的IC50和EC50与pembrolizumab相似，明显低于其他PD-1抑制剂，对PD-1位点有更高的亲和力。 Camrelizumab 在晚期 HCC 中表现出与其他 PD-1 抑制剂相似的有希望的抗肿瘤活性和可接受的安全性。阿帕替尼（一种 VEGFR-2 酪氨酸激酶抑制剂）可以降低卡瑞珠单抗特异性反应性皮肤毛细血管内皮增生 (RCCEP) 的发生率。

关键词：camrelizumab 免疫检查点抑制剂 免疫疗法 肝细胞癌
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感谢孙颖（江苏恒瑞药业有限公司医学部经理）在收集和总结临床前和临床数据方面提供的宝贵支持，感谢天宇（江苏恒瑞药业有限公司医学作家）。 )和Yunjie Yu（原江苏恒瑞药业有限公司员工）提供医学写作支持。
文章亮点

    临床试验正在评估卡瑞珠单抗单药治疗、免疫治疗加靶向治疗、免疫检查点抑制剂加全身化疗以及持续免疫治疗的临床益处。

    未来的研究将侧重于识别和开发对晚期 HCC 中的 camrelizumab 有反应的可靠生物标志物。

利益声明

在过去的 5 年里，孙惠传收到了罗氏、拜耳、默沙东、卫材、恒瑞、信达、TopAlliance、雅培、百济神州、吉利德、泽尔根的酬金和讲课费。

作者与与手稿中讨论的主题或材料有经济利益或经济冲突的任何组织或实体没有其他相关的从属关系或财务参与。这包括就业、咨询、酬金、股票所有权或期权、专家证词、已收到或正在申请的赠款或专利，或特许权使用费。

StephenW

Camrelizumab: an investigational agent for hepatocellular carcinoma
Bin Xu
& Hui-Chuan Sun
Received 22 Nov 2021, Accepted 19 Dec 2021, Accepted author version posted online: 23 Dec 2021

    Download citation https://doi.org/10.1080/13543784.2022.2022121 CrossMark Logo CrossMark

Accepted author version
ABSTRACT
Introduction

: Although many approaches have been used to treat hepatocellular carcinoma (HCC), the clinical benefits were limited, particularly for advanced HCC. However, recent treatments with PD-1/PD-L1 inhibitor monotherapy and its combination with other therapies, have demonstrated remarkable results. Camrelizumab, a selective, humanized, high-affinity IgG4 PD-1 monoclonal antibody, has been approved as a second-line treatment in patients with advanced HCC by NMPA in China.
Areas covered

: This paper introduces anti-PD-1/PD-L1 immunotherapies for advanced HCC and progresses to discuss the pharmacology, safety, and efficacy of camrelizumab in the treatment of advanced HCC. It also considers future research directions for camrelizumab in this setting.
Expert opinion

: The PD-1 binding epitope of camrelizumab is different from other PD-1 inhibitors. The IC50 and EC50 of camrelizumab for inhibiting the binding of PD-1 and PD-L1 is similar to pembrolizumab, is significantly lower than other PD-1 inhibitors, and has a higher affinity for PD-1 site. Camrelizumab exhibits a promising antitumor activity and an acceptable safety profile similar to other PD-1 inhibitors in advanced HCC. Apatinib (a VEGFR-2 tyrosine kinase inhibitor) can reduce the incidence of camrelizumab-specific reactive cutaneous capillary endothelial proliferation (RCCEP).

Keywords: camrelizumabimmune checkpoint inhibitorimmunotherapyhepatocellular carcinoma
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As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

The author thanks Ying Sun (a medical science manager at Jiangsu Hengrui Pharmaceuticals Co., Ltd.) for valuable support in gathering and summarizing pre-clinical and clinical data, and Yu Tian (a medical writer at Jiangsu Hengrui Pharmaceuticals Co., Ltd.) and Yunjie Yu (a former employee of Jiangsu Hengrui Pharmaceuticals Co., Ltd.) for providing medical writing support.
Article Highlights

    Clinical trials are evaluating camrelizumab monotherapy, immunotherapy plus targeted therapies, immune checkpoint inhibitors plus systemic chemotherapy, and clinical benefit of continued immunotherapy treatments.

    Future research will focus on the recognition and development of reliable biomarkers which respond to camrelizumab in advanced HCC.

Declaration of interest

Hui Chuan Sun received honorarium and lecture fees from Roche, Bayer, MSD, Eisai, Hengrui, Innovent, TopAlliance, Abbott, Beigene, Gilead, Zelgen during the last 5 years.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.