A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer

被引:199
作者
Bayliss, Trevor J. [1 ]
Smith, Jeff T.
Schuster, Michael [2 ]
Dragnev, Konstantin H. [1 ]
Rigas, James R. [1 ]
机构
[1] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Comprehens Thorac Oncol Program, Lebanon, NH 03766 USA
[2] SUNY Stony Brook, Hematol Malignancy Program, Stony Brook, NY 11794 USA
关键词
ALD518; anemia; cachexia; C-reactive protein (CRP); epidermal growth factor receptor; interleukin-6; non-small cell lung cancer; GROWTH-FACTOR RECEPTOR; MOLECULAR PREDICTORS; MULTIPLE-MYELOMA; TNF-ALPHA; ANEMIA; INFLAMMATION; IL-6; INTERLEUKIN-6; HEPCIDIN; MECHANISMS;
D O I
10.1517/14712598.2011.627850
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Introduction: Inflammatory pathways may be an important contributor to morbidity and mortality associated with lung cancer. The oncogene-associated inflammatory microenvironment leads to production of inflammatory cytokines such as IL-6. IL-6 is associated with poor prognosis and correlates with debilitating lung-cancer-related symptoms such as fatigue, thromboembolism, cachexia and anemia. IL-6 has been implicated in resistance of lung cancer to EGF inhibitors. A mAb therapy targeting IL-6 may be an effective treatment for the inflammatory microenvironment in lung cancer. Areas covered: An understanding of the inflammatory pathways involved in lung cancer, including the central role of IL-6, and how inflammation affects the course and treatment of lung cancer. The mAb ALD518, which targets IL-6, and its investigational development and use in advanced NSCLC. Preclinical and Phase I and II studies of ALD518 with a focus on NSCLC. How ALD518 could be used in NSCLC in the future. Expert opinion: IL-6-mediated inflammation may contribute to NSCLC-related morbidity and mortality. In preclinical and Phase I and II trials ALD518 targeting IL-6 appears well tolerated and ameliorates NSCLC-related anemia and cachexia. Other clinical outcomes need further study, and may include effects on overall survival, hypercoagulability associated with lung cancer and decreased resistance to EGF-pathway inhibitors.
引用
收藏
页码:1663 / 1668
页数:6
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