Therapeutic antibodies elicited by immunization against TNF-α
Therapeutic antibodies elicited by immunization against TNF-α
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DOI：
10.1038/10878
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发表时间：
1999-07-01
影响因子：
46.9
通讯作者：
Mouritsen, S
中科院分区：
文献类型：
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作者：
Dalum, I;Butler, DM;Mouritsen, S
肿瘤坏死因子-α(TNF-α)在多种慢性炎症性疾病的发病机制中起重要作用。抗肿瘤坏死因子-α的单抗目前被用于治疗类风湿性关节炎和克罗恩病。本文介绍了一种简单有效的主动免疫自身肿瘤坏死因子-α的方法。这种疫苗接种方法导致依赖T细胞的多克隆和可持续的抗肿瘤坏死因子-α自身抗体反应，这种反应在停止加强注射后下降。这些自身抗体是通过注射含有外源免疫优势T辅助表位的经修饰的重组肿瘤坏死因子-α分子而产生的。在用这种分子免疫的小鼠中，实验性恶病质和II型胶原诱导的关节炎的症状得到改善。这些结果表明，接种肿瘤坏死因子-α疫苗可能是治疗类风湿性关节炎和其他慢性炎症性疾病的有效方法。
Tumor necrosis factor-alpha (TNF-alpha) is critically involved in the pathogenesis of several chronic inflammatory diseases. Monoclonal antibodies against TNF-alpha are currently used for the treatment of rheumatoid arthritis and Crohn's disease. This report describes a simple and effective method for active immunization against self TNF-alpha. This vaccination approach leads to a T-cell-dependent polyclonal and sustainable anti-TNF-alpha autoantibody response that declines upon discontinuation of booster injections. The autoantibodies are elicited by injecting modified recombinant TNF-alpha molecules containing foreign immunodominant T-helper epitopes. In mice immunized with such molecules, the symptoms of experimental cachexia and type II collagen-induced arthritis are ameliorated. These results suggest that vaccination against TNF-alpha may be a useful approach for the treatment of rheumatoid arthritis and other chronic inflammatory diseases.