近日,，一個包括莫菲特癌癥中心的研究員在內(nèi)的國際合作研究發(fā)現(xiàn),，20％至25％”給予PD-1抗體治療參加臨床試驗的癌癥患者后會出現(xiàn)一個持久的應(yīng)對BMS-936558治療的應(yīng)答反應(yīng)。 PD-1是一個激活免疫細胞（T細胞）表達的重要的免疫“檢查點”受體,，PD-1參與免疫抑制過程,。
該臨床試驗旨在評估該藥物的抗腫瘤活性和治療的安全性,，其中包括296例癌癥患者參與研究,。研究結(jié)果發(fā)表在New England Journal of Medicine雜志上,。
Antonia說：近期已經(jīng)有很多公司努力開發(fā)治療癌癥的免疫治療方法包括免疫檢查點抑制劑。 腫瘤免疫治療的一個特別挑戰(zhàn)之處在于找到合適的生物標志物,，用于識別病人腫瘤免疫治療效果的生物標記物,。
Antonia說，他們的研究結(jié)果證實腫瘤所表達PD-1配體——PD-L1是一個重要的候選分子標記物,。例如PD-L1陽性腫瘤患者：BMS-936558的反應(yīng)率為36％,，而PD-L1陰性腫瘤患者卻對治療沒有響應(yīng)。其中296人包括非小細胞肺癌,、黑色素瘤或腎細胞癌患者是完全有反應(yīng)或是出現(xiàn)部分反應(yīng),，研究人員得出結(jié)論認為抗PD-1抗體是安全的，癌癥患者的有效反應(yīng)是“持久的”,。
項研究由施貴寶公司贊助,，該公司提供藥物的研究工作與研究設(shè)計、實施和評估研究,。(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
