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抗CD3抗体:迈向临床抗原特异性免疫调节

Anti-CD3 antibodies: towards clinical antigen-specific immunomodulation.

作者信息

Chatenoud Lucienne

机构信息

INSERM U580 IRNEM, Hôpital Necker 161 Rue de Sèvres, 75015 Paris, France.

出版信息

Curr Opin Pharmacol. 2004 Aug;4(4):403-7. doi: 10.1016/j.coph.2004.03.012.

Abstract

Current therapeutic approaches in transplantation and autoimmunity are essentially focused on immunosuppression, which is non-specific (i.e. unrelated to the antigens involved). The major drawback is their relative ineffectiveness in the long term, with the likely risk of recurrence of the pathogenic immune process once the drug is withdrawn necessitating indefinite drug administration; this has attendant problems of recurrent infections and drug toxicity. Instead, CD3-specific monoclonal antibodies possess the unique capacity to induce immunological tolerance: an antigen-specific unresponsiveness in the absence of long-term generalised immunosuppression, as is well-established in experimental models. Clinical application using humanised non-mitogenic CD3-specific antibodies is presently underway. The future challenge will be to define the modalities allowing the widespread application of this strategy through a better understanding of the underlying immune mechanisms.

摘要

目前移植和自身免疫性疾病的治疗方法主要集中在免疫抑制上,这种方法是非特异性的(即与所涉及的抗原无关)。主要缺点是其长期效果相对不佳,一旦停药,致病免疫过程很可能复发,这就需要长期用药;随之而来的问题是反复感染和药物毒性。相反,CD3特异性单克隆抗体具有诱导免疫耐受的独特能力:即在不存在长期全身性免疫抑制的情况下产生抗原特异性无反应性,这在实验模型中已得到充分证实。目前正在进行使用人源化非促有丝分裂CD3特异性抗体的临床应用。未来的挑战将是通过更好地理解潜在的免疫机制来确定允许广泛应用该策略的方式。

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