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程序死亡分子1抗体药物在癌症治疗中的研究进展

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摘要 肿瘤抗原特异性T细胞的功能受到正向和负向两方面的信号调节。肿瘤能够诱导T细胞无能,其主要原因是由于缺乏积极的正向刺激信号,而使得负调免疫机制占主导地位。T细胞上程序死亡分子1(PD-1)的高表达,并与肿瘤细胞的PD-1配体之一(PD-L1)分子相互作用介导了T细胞功能耗竭状态,这是其中非常重要的负调信号通路。临床前癌症模型中,阻断PD-1/PD-L1的相互作用,可以提高抗肿瘤的T细胞反应,进而控制肿瘤进程。目前,靶向PH-1和PD-L1单克隆抗体药物的开发已经取得了非常好的研究进展,并在多种癌症患者的Ⅰ/Ⅱ期临床试验评估中取得了理想的治疗效果。所以,抑制负向免疫调节途径的相关药物的研发,也就成为潜在的、非常有价值的肿瘤免疫治疗方式。
作者 韩向阳 杨庆华 张静
机构地区 山东莱芜钢铁集团有限公司医院药剂科
出处 《中国临床药学杂志》 CAS 2013年第6期391-394,共4页 Chinese Journal of Clinical Pharmacy
关键词 程序死亡分子-1 抗体药物 肿瘤 单克隆抗体
分类号 R730.5 [医药卫生—肿瘤]
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参考文献25

  • 1Parry RV, Chemnitz JM, Franwirth KA, et al. CTLA-4 and PD-1 re- ceptors inhibit T-cell activation by distinct mechanisms[Jl. Mol Cell Bi- ol, 2005, 25(21): 9543.
  • 2Hamanishi J, Mandai M, Iwasaki M, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8 ^+ T lymphocytes are prognostic factors of human ovarian cancer[J]. Proc Nail Acad Sci USA, 2007, 104(9) : 3360.
  • 3Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 im- mtmoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation [ J ]. J Exp Ned, 2000, 192 ( 7 ) : 1027.
  • 4Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death- 1 ligands on dendritic cells enhances T cell activation and eytokine pro- duction[J]. J Immunol, 2003, 170(3): 1257.
  • 5Callahan MK, Wolchok JD. At the bedside: CTLA-4- and PD-l-block- ing antibodies in cancer inmatmotherapy[J]. J Leukoc Biol, 2013,94 (1):41.
  • 6Holmgaard liB, Zamarin D, Murm DH, et al. Indoleamiae 2,3-dioxyge- nase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4[J]. J Exp Med, 2013, 210(7) : 1389.
  • 7O'Day SJ, Maio M, Chiarion-Sileni V, et al. Efficacy and safety ofip- ilimumab monotherapy in patients with pretreated advanced melanoma: a muhicenter single-ann phase Ⅱ study[J]. Ann Oncol, 2010, 21 (8) : 1712.
  • 8Kirkwoed JM, Lorigan P, Hersey P, et al. Phase Ⅱ trial of tremelimum- ab (CP-675,206) in patients with advanced refractory or relapsed melanoma[J]. Clin Cancer Res, 2010, 16(3): 1042.
  • 9He YF, Zhang GM, Wang XH, et al. Blocking programmed death-1 lig- and-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine[J]. J Immunol, 2004, 173(8) : 4919.
  • 10Ahmedzadeh M, Johnson LA, Heemskerk B, et al. Tumor antigen-spe- cific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired[J]. Blood, 2009, 114(8): 1537.

二级参考文献9

  • 1Ye Y,Zhou L,Xie X. Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion[J].Journal of Surgical Oncology,2009.500-504.
  • 2Okazaki T,Honjo T. The PD-1-PD-L pathway in immunological tolerance[J].Trends in Immunology,2006.195-201.
  • 3Zhang G,Hou J,Shi J. Soluble CD276 (B7-H3) is released from monocytes,dendritic cells and activated T cells and is detectable in normal human serum[J].Immunology,2008.538-546.
  • 4Qin W,Hongya W,Yongjing C. Increased OX40 and soluble OX40 ligands in children with Henoch-Schonlein purpura:association with renal involvement[J].Pediatric Allergy and Immunology,2011.54-59.
  • 5Chen Y,Wang Q,Shi B. Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1 (+) cell lines[J].Cytokine,2011.231-238.
  • 6Keir ME,Butte MJ,Freeman GJ. PD-1 and its ligands in tolerance and immunity[J].Annual Review of Immunology,2008.677-704.
  • 7del Rio ML,Buhler L,Gibbons C. PD-1/PD-L1,PD-1/PD-L2,and other co-inhibitory signaling pathways in transplantation[J].Transplant International,2008.1015-1028.
  • 8Dong H,Strome SE,Salomao DR. Tumor-associated B7-H1 promotes T-cell apoptosis:a potential mechanism of immune evasion[J].Nature Medicine,2002,(8):793-800.
  • 9Ascierto PA,Simeone E,Sznol M. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies[J].Seminars in Oncology,2010.508-516.

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中国临床药学杂志
2013年 第6期

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