Nissim A, Chernajovsky Y
Bone and Joint Research Unit, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, Charterhouse Square, London, UK.
Handb Exp Pharmacol. 2008(181):3-18. doi: 10.1007/978-3-540-73259-4_1.
Since the first publication by Kohler and Milstein on the production of mouse monoclonal antibodies (mAbs) by hybridoma technology, mAbs have had a profound impact on medicine by providing an almost limitless source of therapeutic and diagnostic reagents. Therapeutic use of mAbs has become a major part of treatments in various diseases including transplantation, oncology, autoimmune, cardiovascular, and infectious diseases. The limitation of murine mAbs due to immunogenicity was overcome by replacement of the murine sequences with their human counterpart leading to the development of chimeric, humanized, and human therapeutic antibodies. Remarkable progress has also been made following the development of the display technologies, enabling of engineering antibodies with modified properties such as molecular size, affinity, specificity, and valency. Moreover, antibody engineering technologies are constantly advancing to enable further tuning of the effector function and serum half life. Optimal delivery to the target tissue still remains to be addressed to avoid unwanted side effects as a result of systemic treatment while achieving meaningful therapeutic effect.
自科勒（Kohler）和米尔斯坦（Milstein）首次发表关于利用杂交瘤技术生产小鼠单克隆抗体（mAb）以来，单克隆抗体通过提供几乎无限的治疗和诊断试剂来源，对医学产生了深远影响。单克隆抗体的治疗用途已成为包括移植、肿瘤学、自身免疫性疾病、心血管疾病和传染病在内的各种疾病治疗的重要组成部分。通过用人源序列取代鼠源序列克服了鼠源单克隆抗体的免疫原性限制，从而推动了嵌合抗体、人源化抗体和全人治疗性抗体的发展。展示技术的发展也取得了显著进展，使得能够对抗体进行工程改造，赋予其如分子大小、亲和力、特异性和价态等修饰特性。此外，抗体工程技术不断进步，以进一步调节效应器功能和血清半衰期。为了在实现有意义的治疗效果的同时避免全身治疗产生的不良副作用，如何实现向靶组织的最佳递送仍是有待解决的问题。
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