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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2021, Vol. 41 Issue (9): 71-77    DOI: 10.13523/j.cb.2105017
综述     
PD-L1和VEGF双靶点联合阻断治疗的研究进展
赵梦泽1,李凤智2,王鹏银2,李剑2,徐寒梅1,*()
1 中国药科大学生命科学与技术学院 南京 211100
2 天士力生物医药股份有限公司 上海 201203
Research Progress of Dual-target Blocking Therapy of PD-L1 and VEGF
ZHAO Meng-ze1,LI Feng-zhi2,WANG Peng-yin2,LI Jian2,XU Han-mei1,*()
1 Life Science and Technology College, China Pharmaceutical University, Nanjing 211100, China
2 Tasly Biopharmaceuticals Co., Ltd., Shanghai 201203, China
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摘要：

免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)通过阻断负调控免疫信号激活宿主抗肿瘤免疫反应。临床试验表明,ICIs的治疗能够明显引起部分晚期癌症患者的肿瘤消退。在临床实践中,ICIs治疗的一个主要问题是药物应答率低。尽管PD-L1表达、错配修复缺陷、肿瘤浸润性淋巴细胞状态等多种预测生物标志物已被用于筛选对治疗有应答的患者,但ICIs单药治疗的耐药性仍存在。近期研究表明,联合抗VEGF治疗可以减轻ICIs的耐药性。VEGF能抑制肿瘤生长和转移所必需的血管生成,同时能够对肿瘤免疫微环境进行重编程,减轻ICIs的耐药性。目前已针对此双靶点的联合治疗开展了很多临床试验,并获得了令人振奋的结果。对抗PD-L1联合抗VEGF治疗的作用机制以及PD-L1/VEGF联合阻断治疗的临床研究进行了综述汇总。
关键词： PD-L1;  VEGF;  肿瘤免疫微环境    
Abstract:

Immune checkpoint inhibitor (immune checkpoint inhibitors,ICIs) activates host anti-tumor immune response by blocking negative regulatory immune signals. Clinical trials have shown that the treatment of ICIs can significantly cause tumor regression in some patients with advanced cancer. In clinical practice, one of the main problems in ICIs treatment is the low response rate. Although various predictive biomarkers such as PD-L1 expression, mismatch repair deficiency, and tumor-infiltrating lymphocyte status have been used to screen patients who respond to treatment, the resistance of ICIs monotherapy still exists. Recent studies have shown that combined anti-VEGF therapy can reduce the resistance of ICIs. VEGF can inhibit angiogenesis necessary for tumor growth and metastasis, while it can reprogram the tumor immune microenvironment and reduce the resistance of ICIs. Many clinical trials have been carried out for the combination therapy of these two targets, and exciting results have been obtained. The mechanism of action of anti-PD-L1 combined with anti-VEGF therapy and the clinical studies of PD-L1/VEGF combined blocking therapy were reviewed and summarized.
Key words: PD-L1    VEGF    Tumor immune microenvironment
收稿日期: 2021-05-10 出版日期: 2021-09-30
ZTFLH:  Q819  
通讯作者: 徐寒梅     E-mail: 1037714870@qq.com
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赵梦泽
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引用本文:

赵梦泽,李凤智,王鹏银,李剑,徐寒梅. PD-L1和VEGF双靶点联合阻断治疗的研究进展[J]. 中国生物工程杂志, 2021, 41(9): 71-77.

ZHAO Meng-ze,LI Feng-zhi,WANG Peng-yin,LI Jian,XU Han-mei. Research Progress of Dual-target Blocking Therapy of PD-L1 and VEGF. China Biotechnology, 2021, 41(9): 71-77.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2105017    或    https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I9/71

联合药物 国家 适应证 首要治疗终点 NCT ID 参考文献
Bevacizumab +Atezolizumab 丹麦、芬兰和法国 宫颈癌 OS NCT03556839 [41]
Bevacizumab +Atezolizumab 澳大利亚、加拿大和巴西 原发性肾细胞癌 PFS in PD-L1+; OS in ITT NCT02420821 [42]
Bevacizumab+Atezolizumab+chemo 阿根廷和澳大利亚 肾细胞癌 PFS;OS NCT02366143 [43]
Bevacizumab+Atezolizumab+chemo 德国 复发性卵巢癌 PFS;OS NCT03353831 [44]
Bevacizumab +Atezolizumab 澳大利亚、奥地利和比利时 肝细胞癌 RFS NCT04102098 [45]
Bevacizumab +Atezolizumab 澳大利亚、加拿大和中国 肝细胞癌 PFS;OS NCT03434379 [46]
Bevacizumab+Atezolizumab+chemo 美国 结直肠癌 PFS NCT02997228 N/A
Bevacizumab+Atezolizumab+chemo 中国 非小细胞肺癌 PFS in ITT NCT04194203 N/A
Bevacizumab+Atezolizumab+chemo 比利时、法国和意大利 间皮瘤 PFS;OS NCT03762018 N/A
联合药物 国家 适应证 首要治疗终点 NCT ID 参考文献
Bevacizumab+Atezolizumab+chemo 澳大利亚、奥地利和比利时 卵巢癌;输卵管癌;腹膜肿瘤 PFS in PD-L1+; PFS in ITT; OS in PD-L1+; OS in ITT NCT03038100 [47]
Bevacizumab+Atezolizumab+chemo 奥地利、比利时和捷克 卵巢癌 PFS NCT02891824 N/A
Bevacizumab +Atezolizumab N/A 肾细胞癌 Percentage of participants with adverse events NCT03693573 N/A
Bevacizumab+Atezolizumab+chemo 韩国 非小细胞肺癌 PFS NCT03991403 N/A
Bevacizumab +Atezolizumab N/A 肝细胞癌 Number of participants with grade 3-5 NCI CTCAE v.5 bleeding/haemorrhage NCT04487067 N/A
表1  贝伐单抗与阿替利珠单抗联合治疗Ⅲ期临床试验的数据报告
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