近日，一个包括莫菲特癌症中心的研究员在内的国际合作研究发现，20％至25％”给予PD-1抗体治疗参加临床试验的癌症患者后会出现一个持久的应对BMS-936558治疗的应答反应。 PD-1是一个激活免疫细胞（T细胞）表达的重要的免疫“检查点”受体，PD-1参与免疫抑制过程。
该临床试验旨在评估该药物的抗肿瘤活性和治疗的安全性，其中包括296例癌症患者参与研究。研究结果发表在New England Journal of Medicine杂志上。
Antonia说：近期已经有很多公司努力开发治疗癌症的免疫治疗方法包括免疫检查点抑制剂。 肿瘤免疫治疗的一个特别挑战之处在于找到合适的生物标志物，用于识别病人肿瘤免疫治疗效果的生物标记物。
Antonia说，他们的研究结果证实肿瘤所表达PD-1配体——PD-L1是一个重要的候选分子标记物。例如PD-L1阳性肿瘤患者：BMS-936558的反应率为36％，而PD-L1阴性肿瘤患者却对治疗没有响应。其中296人包括非小细胞肺癌、黑色素瘤或肾细胞癌患者是完全有反应或是出现部分反应，研究人员得出结论认为抗PD-1抗体是安全的，癌症患者的有效反应是“持久的”。
项研究由施贵宝公司赞助，该公司提供药物的研究工作与研究设计、实施和评估研究。(生物谷：Bioon.com）
doi:10.1056/NEJMoa1200690
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Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer
Suzanne L. Topalian et al
Background
Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1.
Methods
We enrolled patients with advanced melanoma, non–small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti–PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred.
Results
A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non–small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non–small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1–PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1–negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1–positive tumors had an objective response (P=0.006).
Conclusions
Anti–PD-1 antibody produced objective responses in approximately one in four to one in five patients with non–small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov
