BioNTech, Mainz, Germany.
Cluster of Individualized Immunointervention (CI3), Mainz, Germany.
Nat Med. 2017 Jul;23(7):815-817. doi: 10.1038/nm.4356. Epub 2017 Jun 12.
The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.
双特异性 T 细胞接合抗体的潜力受到制造挑战和血清半衰期短的限制。我们通过用体外转录的药理学优化、核苷修饰的 mRNA 治疗小鼠来规避这些限制，该 mRNA 编码抗体。我们实现了抗体的持续内源性合成，其消除晚期肿瘤的效果与相应的纯化双特异性抗体一样有效。由于制药 mRNA 的制造速度很快，这种方法可以加速新型双特异性抗体的临床开发。
