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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  2019, Vol. 39 Issue (2): 62-73    DOI: 10.13523/j.cb.20190208
精准医疗与伴随诊断专刊     
肿瘤精准免疫诊断综合评估
杨琳,李勇超,张腾华,邓乙晓,杨锦,高志博()
深圳裕策生物科技有限公司 深圳 518081
Comprehensive Evaluation is needed for Precision Diagnosis in Cancer Immunotherapies
Lin YANG,Yong-chao LI,Teng-hua ZHANG,Yi-xiao DENG,Jin YANG,Zhi-bo GAO()
Yuce Biotechnology Co.,Ltd,Shenzhen 518081,China
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摘要：

近年来,肿瘤免疫治疗(cancer immunotherapies)已成为晚期恶性肿瘤治疗的重要手段之一。肿瘤免疫治疗并不直接攻击癌细胞,而是通过调节人体自身免疫系统来抗击肿瘤,有望像抗生素改变抗感染治疗一样改变肿瘤治疗范式。抗PD-1/L1和抗CTLA-4抗体药物作为肿瘤免疫治疗的代表药物,使晚期癌症患者五年生存率达成了数倍的提升,被认为是真正有希望治愈癌症的治疗方式。然而,肿瘤免疫治疗只对部分患者有效,并且存在耐药、超进展、不良反应等问题。如何准确筛选出最有可能从治疗中获益的人群成为肿瘤免疫治疗研究中的一个重大挑战。目前有多个与免疫治疗相关的生物标志物正在研究中,并且有望被用于临床筛选治疗获益人群;但这些生物标记物也存在很多缺陷。未来,围绕免疫治疗敏感性和副反应的多项指标综合评估可能成为一个趋势。
关键词： 肿瘤;  免疫治疗;  精准诊断;  免疫综合评估    
Abstract:

Cancer immunotherapies has become one of the important approaches in advanced malignant tumor treatments. The immunotherapies attack tumors by reinvigorating the human immune system, which will change the paradigm of cancer treatment. The immunotherapies, including anti-PD-1/L1 and anti-CTLA-4 antibodies, have improved the five-year survival rate of patients with malignant tumors, and have been recognized as the most promising treatments to cure cancer. However, only a subset of patients benefits from the immunotherapy, and there are problems such as drug resistance, hyperprogression disease, and immune-related adverse events. Thus, the early selection of the most sensitive patients is key, and the development of predictive biomarkers is one of the biggest challenges of cancer immunotherapy development. Many biomarkers are under investigation, and they are potentially applicable to the clinical selection of patients for immunotherapies, but each has limited utility. Comprehensive evaluation of multiple indicators around the sensitivity and the adverse events of immunotherapies will be the direction of the future. In this article, we will review the research progress in cancer immunotherapies and comprehensive evaluation of precision cancer diagnosis.
Key words: Cancer immunotherapy    Precision diagnosis    Comprehensive evaluation
收稿日期: 2019-01-10 出版日期: 2019-03-26
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杨琳
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张腾华
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杨锦
高志博

引用本文:

杨琳,李勇超,张腾华,邓乙晓,杨锦,高志博. 肿瘤精准免疫诊断综合评估[J]. 中国生物工程杂志, 2019, 39(2): 62-73.

Lin YANG,Yong-chao LI,Teng-hua ZHANG,Yi-xiao DENG,Jin YANG,Zhi-bo GAO. Comprehensive Evaluation is needed for Precision Diagnosis in Cancer Immunotherapies. China Biotechnology, 2019, 39(2): 62-73.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20190208    或    https://manu60.magtech.com.cn/biotech/CN/Y2019/V39/I2/62

药企 药物名 商品名 靶点 获批适应
症数量		 FDA批准适应症 NMPA
批准适应症
百时美
施贵宝		 伊匹木单抗
IPILIMUMAB		 YERVOY CTLA-4 2 黑色素瘤、肾细胞癌
百时美
施贵宝		 纳武利尤单抗
NIVOLUMAB		 欧狄沃
OPDIVO		 PD-1 9 恶性黑色素瘤、非小细胞肺癌、肾细胞癌、经典型霍奇金淋巴癌、头颈部鳞癌、尿路上皮癌、MSI-H/DMMR转移性结直肠癌、肝细胞癌、小细胞肺癌 非小细
胞肺癌
默沙东 帕博利珠单抗
PEMBROLIZUMAB		 可瑞达
KEYTRUDA		 PD-1 11 黑色素瘤、非小细胞肺癌、头颈部鳞癌、经典型霍奇金淋巴癌、尿路上皮癌,MSI-H/DMMR实体瘤、胃癌/胃食管结合部腺癌、宫颈癌、纵隔大B细胞淋巴瘤、肝细胞癌、默克尔细胞癌 黑色素瘤
赛诺菲&
再生元		 CEMIPLIMAB-
RWLC		 LIBTAYO PD-1 1 皮肤鳞状细胞癌
罗氏 ATEZOLIZUMAB TECENTRIQ PD-L1 2 尿路上皮癌、非小细胞肺癌
默克&辉瑞 AVELUMAB BAVENCIO PD-L1 2 转移性默克尔细胞癌、尿路上皮癌
阿斯利康 DURVALUMAB IMFINZI PD-L1 2 尿路上皮癌、非小细胞肺癌
君实生物 特瑞普利单抗 拓益 PD-1 1 黑色素瘤
信达生物 信迪利单抗 达伯舒 PD-1 1 霍奇金淋巴瘤
表1  已获批的免疫检查点抑制剂药物
图1  液体活检指导免疫治疗的潜在生物标志物
图2  肿瘤免疫循环[61]
图3  个体化肿瘤免疫综合评价模型框架
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