Diamant Eran, Torgeman Amram, Ozeri Eyal, Zichel Ran
Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel.
Toxins (Basel). 2015 May 29;7(6):1854-81. doi: 10.3390/toxins7061854.
Monoclonal antibodies (MAbs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. Nevertheless, MAbs potency is still relatively low when compared to conventional polyclonal Ab preparations. Moreover, the efficacy of an individual neutralizing MAb may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. These limitations of individual neutralizing MAbs can be overcome by using oligoclonal combinations of several MAbs with different specificities to the target antigen. Studies conducted in our lab and by others show that such combined MAb preparation may present substantial synergy in its potency over the calculated additive potency of its individual MAb components. Moreover, oligoclonal preparation is expected to be better suited to compensating for reduced efficacy due to epitope variation. In this review, the synergistic neutralization properties of combined oligoclonal Ab preparations are described. The effect of Ab affinity, autologous Fc fraction, and targeting a critical number of epitopes, as well as the unexpected contribution of non-neutralizing clones to the synergistic neutralizing effect are presented and discussed.
单克隆抗体（MAb）是增长最快的治疗药物之一，正被开发用于广泛的适应症，包括中和毒素、细菌和病毒。然而，与传统的多克隆抗体制剂相比，单克隆抗体的效力仍然相对较低。此外，在感染因子的突变体或亚型中，其靶表位可能不存在或发生修饰，这可能会显著阻碍单个中和单克隆抗体的疗效。通过使用几种对靶抗原具有不同特异性的单克隆抗体的寡克隆组合，可以克服单个中和单克隆抗体的这些局限性。我们实验室和其他机构进行的研究表明，这种联合单克隆抗体制剂在效力上可能比其单个单克隆抗体成分的计算加和效力具有显著的协同作用。此外，预计寡克隆制剂更适合于补偿由于表位变异导致的疗效降低。在这篇综述中，描述了联合寡克隆抗体制剂的协同中和特性。本文介绍并讨论了抗体亲和力、自身Fc片段、靶向关键数量表位的影响，以及非中和克隆对协同中和作用的意外贡献。
