Pèlegrin André, Robert Bruno
Institut de recherche en cancérologie de Montpellier (IRCM), Montpellier, F-34298, France ; Inserm U896, Montpellier, F-34298, France.
Med Sci (Paris). 2009 Dec;25(12):1155-8. doi: 10.1051/medsci/200925121155.
Monoclonal antibodies have emerged as a very successful class of therapeutic agents. In their native format, monoclonal antibodies are monospecific in that they recognize only one epitope, but their Fc domain also binds to FcfR-expressing cells. Attempts to improve the cytotoxicity of antibodies, particularly in the cancer field, have led to the design of bispecific antibodies: this can occur through various strategies, such as quadroma, thioether-linked Fab' gamma fragments or genetic engineering. Such bispecific antibodies have been developped to enhance immunotherapy, by bridging tumor cells and T cells, or radioimmunotherapy by combining bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells. Multiple further applications can be envisaged such as targeting two different antigens on the same cell, or two epitopes of the same antigen. Although progresses have been slowed by technical constraints, there is little doubt that this class of novel antibodies derivatives will experience a promising development.
单克隆抗体已成为一类非常成功的治疗药物。以其天然形式，单克隆抗体具有单特异性，即它们仅识别一个表位，但其Fc结构域也与表达FcfR的细胞结合。在癌症领域，尝试提高抗体的细胞毒性导致了双特异性抗体的设计：这可以通过多种策略实现，如四瘤、硫醚连接的Fab'γ片段或基因工程。此类双特异性抗体已被开发用于增强免疫疗法，通过连接肿瘤细胞和T细胞，或通过将双特异性抗体与放射性标记的二价半抗原结合来增强放射免疫疗法，这些放射性标记的二价半抗原与靶细胞协同结合。还可以设想多种进一步的应用，例如靶向同一细胞上的两种不同抗原，或同一抗原的两个表位。尽管进展因技术限制而放缓，但毫无疑问，这类新型抗体衍生物将有一个充满希望的发展。
