Cytos Biotechnology AG, CH-8952 Zurich-Schlieren, Switzerland.
Immunotherapy. 2010 Jul;2(4):561-74. doi: 10.2217/imt.10.30.
Pathology in most chronic inflammatory diseases is characterized by an imbalance in cytokine expression. Targeting cytokines with monoclonal antibodies has proven to be a highly effective treatment. However, monoclonal antibody therapy has disadvantages such as high production costs, generation of antimonoclonal antibodies and the inconvenience of frequent injections. Therapeutic vaccines have the potential to overcome these limitations. The aim of active vaccination is to induce B-cell responses and obtain autoantibodies capable of neutralizing the interaction of the targeted cytokine with its receptor. In order to achieve this, therapeutic vaccines need to circumvent the potent tolerance mechanisms that exist to prevent immune responses against self-molecules. This article focuses on the tolerance mechanisms of the B- and T-cell compartments and how these may be manipulated to obtain high-affinity autoantibodies without inducing potentially dangerous autoreactive T-cell responses.
大多数慢性炎症性疾病的病理学特征是细胞因子表达失衡。用单克隆抗体靶向细胞因子已被证明是一种非常有效的治疗方法。然而，单克隆抗体治疗存在生产成本高、产生抗单克隆抗体和频繁注射不便等缺点。治疗性疫苗有可能克服这些限制。主动疫苗接种的目的是诱导 B 细胞反应，并获得能够中和靶向细胞因子与其受体相互作用的自身抗体。为了实现这一目标，治疗性疫苗需要规避存在的强大耐受机制，以防止针对自身分子的免疫反应。本文重点介绍 B 细胞和 T 细胞区室的耐受机制，以及如何操纵这些机制以获得高亲和力的自身抗体，而不诱导潜在危险的自身反应性 T 细胞反应。
