Despite the success of monoclonal antibodies (mAbs) to treat some disorders, the monospecific molecular entity of mAbs as well as the presence of multiple factors and pathways involved in the pathogenesis of disorders, such as various malignancies, infectious diseases, and autoimmune disorders, and resistance to therapy have restricted the therapeutic efficacy of mAbs in clinical use. Bispecific antibodies (bsAbs), by concurrently recognizing two targets, can partly circumvent these problems. Serial killing of tumor cells by bsAb-redirected T cells, simultaneous blocking of two antigens involved in the HIV-1 infection, and concurrent targeting of the activating and inhibitory receptors on B cells to modulate autoimmunity are part of the capabilities of bsAbs. After designing and developing a large number of bsAbs for years, catumaxomab, a full-length bsAb targeting EpCAM and CD3, was approved in 2009 to treat EpCAM-positive carcinomas besides blinatumomab, a bispecific T cell engager antibody targeting CD19 and CD3, which was approved in 2014 to treat relapsed or refractory acute lymphoblastic leukemia. Furthermore, approximately 60 bsAbs are under investigation in clinical trials. The current review aims at portraying different formats of the single-chain variable fragment (scFv)-based bsAbs and shedding light on the scFv-based bsAbs in preclinical development, different phases of clinical trials, and the market.

尽管单克隆抗体 (mAb) 成功治疗了一些疾病，但 mAb 的单特异性分子实体以及涉及疾病发病机制的多种因素和途径的存在，例如各种恶性肿瘤、传染病和自身免疫性疾病，治疗耐药性限制了单克隆抗体在临床应用中的治疗效果。双特异性抗体（bsAbs）通过同时识别两个靶标，可以部分规避这些问题。bsAb 重定向的 T 细胞连续杀伤肿瘤细胞、同时阻断 HIV-1 感染中涉及的两种抗原，以及同时靶向 B 细胞上的激活和抑制受体以调节自身免疫，这些都是 bsAb 功能的一部分。经过多年设计和开发大量双特异性抗体，卡妥索单抗（一种针对 EpCAM 和 CD3 的全长双特异性抗体）于 2009 年被批准用于治疗 EpCAM 阳性癌症，此外还有 blinatumomab（一种针对 CD19 和 CD3 的双特异性 T 细胞接合抗体）。 2014年获批用于治疗复发性或难治性急性淋巴细胞白血病。此外，大约 60 种双特异性抗体正在临床试验中进行研究。当前的综述旨在描述基于单链可变片段（scFv）的双抗体的不同形式，并阐明基于单链可变片段（scFv）的双抗体在临床前开发、临床试验的不同阶段和市场中的情况。