美国抗PD？2012年六月美国Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center的科学家在顶级杂志The new england journal of medicine发表文章，宣布他们研制的抗 programmed death 1 (PD-1)抗体对 黑色素 瘤、非小细胞肺癌、肾癌患者都有明显的抗肿瘤效果。预示该抗体药物将来的市场前景广大。 PD-1是T细胞表面的抑制性受体，他们研制的BMS-936558新型抗PD-1抗体可以阻断PD-1对T细胞的抑制作用，从而激活肿瘤患者体内的免疫效应细胞杀瘤效应。 以下是该文章的摘要： Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer 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 anti- body 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 con- sistent 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. (Fund- ed by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.)查看更多7个回答 . 15人已关注
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