New immunosuppressive approaches: Oral administration of CD3-specific antibody to treat autoimmunity
New immunosuppressive approaches: Oral administration of CD3-specific antibody to treat autoimmunity
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DOI：
10.1016/j.jns.2008.07.027
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发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Weiner, Howard L.
中科院分区：
文献类型：
--
作者：
Ochi, Hirofumi;Abraham, Michal;Weiner, Howard L.
自身免疫性疾病免疫治疗的主要目标之一是诱导介导免疫耐受的调节性T细胞。体外给药抗cd3单克隆抗体是一种被批准的人类移植治疗方法，对自身免疫性糖尿病有效。我们发现口服抗cd3单克隆抗体在肠道中具有生物活性，并且在疾病诱发之前和疾病高度时抑制实验性自身免疫性脑脊髓炎。口服抗cd3抗体通过诱导一种独特的调节性T细胞发挥作用，其特征是细胞表面的潜伏期相关肽（LAP），该细胞通过tgf - β依赖机制在体内和体外发挥作用。口服抗体不会产生细胞因子释放综合征等副作用，因此口服抗cd3抗体在临床上适用于慢性治疗。这些发现确定了一种新的和强大的免疫方法，广泛适用于治疗人类自身免疫性疾病。(C) 2008 Elsevier B.V.版权所有
One of the major goals for the immunotherapy Of autoimmune diseases is the induction of regulatory T cells that mediate immunologic tolerance. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We have found that oral administration of anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental autoimmune encephalomyelitis both prior to disease induction and at the height of disease. Oral anti-CD3 antibody acts by inducing a unique type of regulatory T cell characterized by latency-associated peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF-beta dependent mechanism. Orally delivered antibody would not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. These findings identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions. (C) 2008 Elsevier B.V. All rights reserved.