Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
J Drug Target. 2020 Dec;28(10):1018-1033. doi: 10.1080/1061186X.2020.1772796. Epub 2020 Jun 9.
Monoclonal antibodies (mAbs) are a swiftly growing class of targeted therapeutics for malignancies. After their first advent, the antibody (Ab) engineering trail has shown an evolutionary trajectory - from the rodent-derived Abs to the chimeric, humanised and fully human Abs with higher efficacy and lower/no immunotoxicity. Despite possessing great clinical potentials, several reports have highlighted that monospecific mAbs, even with high-affinity, often fail to induce sufficient immunologic responses. The full activation of the immune system demands cooperative interactions of immunotherapies with target antigen (Ag) towards functional avidity. Although the monospecific mAbs show affinity to a target Ag, they often fail to render sufficient avidity necessary for the activation of intracellular signalling mechanisms and the provocation of the immune system. Thus, various Ab/non-Ab scaffolds with much greater therapeutic impacts have been engineered based on the adjustment of their affinity and avidity balance. Novel multivalent Ab scaffolds (e.g. MDX-447, MT110, CD20Bi, TF2 and FBTA05) and mimetic Abs (e.g. adnectin, DARPins and ecallantide) offer improved pharmacokinetic and pharmacodynamic properties. Here, we discuss the avidity and multivalency and provide comprehensive insights into advanced Ab scaffolds used for immunotargeting and therapy of cancer.
单克隆抗体 (mAbs) 是一类针对恶性肿瘤的快速发展的靶向治疗药物。自首次问世以来，抗体 (Ab) 工程技术已经显示出一种进化轨迹——从鼠源性 Ab 到嵌合、人源化和全人源 Ab，具有更高的疗效和更低/无免疫毒性。尽管具有巨大的临床潜力，但有几项报告强调指出，即使具有高亲和力，单特异性 mAbs 也常常无法诱导足够的免疫反应。免疫系统的完全激活需要免疫疗法与靶抗原 (Ag) 协同作用，以达到功能亲和力。尽管单特异性 mAbs 与靶 Ag 具有亲和力，但它们常常无法产生足够的亲和力来激活细胞内信号机制并引发免疫系统。因此，已经基于调整其亲和力和亲和力平衡来设计各种具有更大治疗影响的 Ab/非 Ab 支架。新型多价 Ab 支架（例如 MDX-447、MT110、CD20Bi、TF2 和 FBTA05）和模拟 Ab（例如 adnectin、DARPins 和 ecallantide）提供了改善的药代动力学和药效学特性。在这里，我们讨论了亲和力和多价性，并提供了对用于癌症免疫靶向和治疗的先进 Ab 支架的全面了解。
