Department of Antibody Engineering, Genentech, Inc., South San Francisco, California, USA.
Nat Biotechnol. 2013 Aug;31(8):753-8. doi: 10.1038/nbt.2621. Epub 2013 Jul 7.
By enabling the simultaneous engagement of two distinct targets, bispecific antibodies broaden the potential utility of antibody-based therapies. However, bispecific-antibody design and production remain challenging, owing to the need to incorporate two distinct heavy and light chain pairs while maintaining natural nonimmunogenic antibody architecture. Here we present a bispecific-antibody production strategy that relies on co-culture of two bacterial strains, each expressing a half-antibody. Using this approach, we produce 28 unique bispecific antibodies. A bispecific antibody against the receptor tyrosine kinases MET and EGFR binds both targets monovalently, inhibits their signaling, and suppresses MET and EGFR-driven cell and tumor growth. Our strategy allows rapid generation of bispecific antibodies from any two existing antibodies and yields milligram to gram quantities of bispecific antibodies sufficient for a wide range of discovery and preclinical applications.
双特异性抗体能够同时结合两个不同的靶点，从而拓宽了抗体疗法的应用潜力。然而，由于需要同时结合两个不同的重链和轻链对，同时保持天然的非免疫原性抗体结构，因此双特异性抗体的设计和生产仍然具有挑战性。在这里，我们提出了一种双特异性抗体生产策略，该策略依赖于两种细菌菌株的共培养，每种细菌菌株都表达一半抗体。使用这种方法，我们生产了 28 种独特的双特异性抗体。一种针对受体酪氨酸激酶 MET 和 EGFR 的双特异性抗体以单价结合两个靶标，抑制其信号传导，并抑制 MET 和 EGFR 驱动的细胞和肿瘤生长。我们的策略允许从任何两种现有抗体快速生成双特异性抗体，并产生毫克到克级别的双特异性抗体，足以满足广泛的发现和临床前应用。
