Carter P, Ridgway J, Zhu Z
Department of Molecular Oncology, Genentech Inc., South San Francisco, CA 94080, USA.
J Hematother. 1995 Oct;4(5):463-70. doi: 10.1089/scd.1.1995.4.463.
The clinical potential of bispecific antibodies (BsAb) has been hindered by the difficulty of obtaining clinical grade material, together with the immunogenicity of rodent-derived BsAb in patients. The supply issue is being directly addressed by recombinant methods for BsAb fragment production reviewed here. The immunogenicity issue will likely be overcome by the use of humanized or human antibodies. Currently, three technologies appear suitable for the production of BsAb fragments for clinical applications: BsF(ab')2 assembled from Fab' fragments expressed in Escherichia coli, BsF(ab')2 assembled using leucine zippers, and diabodies.
双特异性抗体(BsAb)的临床应用潜力受到获取临床级材料困难以及啮齿动物来源的BsAb在患者体内具有免疫原性的阻碍。本文所综述的重组方法可直接解决BsAb片段生产中的供应问题。使用人源化或人抗体可能会克服免疫原性问题。目前,有三种技术似乎适用于生产临床应用的BsAb片段:由在大肠杆菌中表达的Fab'片段组装而成的BsF(ab')2、利用亮氨酸拉链组装的BsF(ab')2以及双体。