Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Madrid, Spain.
Trends Biotechnol. 2010 Jul;28(7):355-62. doi: 10.1016/j.tibtech.2010.03.007. Epub 2010 May 4.
Evolutionary pressure has selected antibodies as key immune molecules acting against foreign pathogens. The development of monoclonal antibody technology has allowed their widespread use in research, real-time diagnosis and treatment of multiple diseases, including cancer. However, compared with hematologic malignancies, solid tumors have often proven to be relatively resistant to antibody-based therapies. In an attempt to improve the tumor-targeting efficacy of antibodies, new formats with modified, multivalent properties have been generated. Initially, these formats imitated the structure of native IgG, creating mostly monospecific, bivalent antibodies. Recently, novel trivalent antibodies have been developed to maximize tumor targeting capabilities through enhanced biodistribution and functional affinity. We review recent advances in the engineering of multivalent antibodies and further discuss their promise as agents for in vivo diagnostics and therapy.
进化压力选择了抗体作为对抗外来病原体的关键免疫分子。单克隆抗体技术的发展使得它们在研究、实时诊断和治疗多种疾病（包括癌症）方面得到了广泛应用。然而，与血液系统恶性肿瘤相比，实体瘤通常对基于抗体的治疗具有相对抗性。为了提高抗体的肿瘤靶向效果，已经产生了具有修饰的、多价特性的新型格式。最初，这些格式模仿了天然 IgG 的结构，主要产生单特异性、二价抗体。最近，开发了新型三价抗体，通过增强生物分布和功能亲和力来最大限度地提高肿瘤靶向能力。我们综述了多价抗体工程的最新进展，并进一步讨论了它们作为体内诊断和治疗剂的前景。
