Delavallée Laure, Assier Eric, Denys Anne, Falgarone Géraldine, Zagury Jean-François, Muller Sylvianne, Bessis Natacha, Boissier Marie-Christophe
Institut National de la Sante et de la Recherche Medicale (Inserm), Bobigny, France.
Ann Med. 2008;40(5):343-51. doi: 10.1080/07853890801995298.
Most autoimmune diseases have an unknown etiology, but all involve cytokines cascade in their development. At the present time, several cytokines have been identified as major targets in various autoimmune diseases, involving the development of monoclonal antibodies (MAbs) against those cytokines. Even if MAbs are indeed efficient, the passive immunotherapies also present some disadvantages and are expensive. To counter this, several strategies have been developed, including active immunotherapy, based on the vaccination principle. The aim of such a strategy is to induce a B cell response and to obtain autoantibodies able to neutralize the interaction of the self-cytokine with its receptor. To that purpose, cytokines (entire or peptide) are either coupled with a protein-carrier or virus-like particle, or modified with foreign Th cell epitopes. DNA vaccination can also be used with cytokine sequences. This review focuses on the different vaccination strategies with cytokines (including Tumor Necrosis Factor (TNF)alpha, Interleukin-1beta (IL-1beta), IL-17) in different autoimmune diseases in preclinical studies; the benefit/risk ratio of such a strategy and the present development of clinical trials in some autoimmune diseases are also discussed.
大多数自身免疫性疾病的病因不明，但在其发展过程中均涉及细胞因子级联反应。目前，已确定几种细胞因子是各种自身免疫性疾病的主要靶点，涉及针对这些细胞因子开发单克隆抗体（MAb）。即使单克隆抗体确实有效，被动免疫疗法也存在一些缺点且成本高昂。为应对这一问题，已开发出多种策略，包括基于疫苗接种原理的主动免疫疗法。这种策略的目的是诱导B细胞反应，并获得能够中和自身细胞因子与其受体相互作用的自身抗体。为此，细胞因子（完整的或肽段）要么与蛋白质载体或病毒样颗粒偶联，要么用外来辅助性T细胞表位进行修饰。细胞因子序列也可用于DNA疫苗接种。本综述重点关注临床前研究中针对不同自身免疫性疾病使用细胞因子（包括肿瘤坏死因子（TNF）α、白细胞介素-1β（IL-1β）、IL-17）的不同疫苗接种策略；还讨论了该策略的效益/风险比以及一些自身免疫性疾病临床试验的当前进展。
