Fanger M W, Morganelli P M, Guyre P M
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756.
Crit Rev Immunol. 1992;12(3-4):101-24.
Bispecific antibodies--molecules combining two different antigenic specificities--are currently being developed as new agents for immunotherapy and for basic studies in cell biology. Bispecific antibodies (BsAb) are prepared by chemically linking two different monoclonal antibodies or by fusing two hybridoma cell lines to produce a hybrid-hybridoma. Both of these approaches present challenges with respect to yield and purity that should eventually be solved through newer molecular genetic approaches. BsAb have been used to demonstrate that specific surface molecules can trigger leukocytes to either phagocytose or kill tumor cells, viruses, parasites, and infected cells. Such trigger molecules include CD3 on T lymphocytes and Fc receptors for IgG on monocytes, macrophages, and natural killer cells. BsAb have also been used experimentally to localize toxins to tumor sites and fibrinolytic agents to areas of thrombosis, to study the molecular specificity of particular receptors, and as adjuvants in in vitro models of vaccines for infectious disease. The limited clinical trials that have occurred to date, primarily for therapy of tumors, suggest that BsAb may offer considerable promise for therapeutic applications, including cancer, heart disease, infectious disease, allergy, and autoimmunity.
双特异性抗体——结合两种不同抗原特异性的分子——目前正作为免疫治疗的新型药物以及细胞生物学基础研究的工具进行研发。双特异性抗体（BsAb）可通过化学连接两种不同的单克隆抗体或融合两种杂交瘤细胞系以产生杂交杂交瘤来制备。这两种方法在产量和纯度方面都面临挑战，最终应通过更新的分子遗传学方法来解决。BsAb已被用于证明特定的表面分子可触发白细胞吞噬或杀死肿瘤细胞、病毒、寄生虫和受感染细胞。此类触发分子包括T淋巴细胞上的CD3以及单核细胞、巨噬细胞和自然杀伤细胞上的IgG Fc受体。BsAb还被用于实验性地将毒素定位到肿瘤部位，将纤溶酶原激活剂定位到血栓形成区域，研究特定受体的分子特异性，以及作为传染病疫苗体外模型中的佐剂。迄今为止进行的有限临床试验主要针对肿瘤治疗，结果表明BsAb在包括癌症、心脏病、传染病、过敏和自身免疫性疾病在内的治疗应用中可能具有巨大潜力。
