McSAF, 1 rue Claude Thion, 37000 Tours, France.
Department of Pathology, University of Tours, BIP INRA UMR1282 ISP, CHU de Tours, avenue de la République, 37170 Chambray-lès-tours, France.
Bioconjug Chem. 2022 Feb 16;33(2):418-426. doi: 10.1021/acs.bioconjchem.2c00015. Epub 2022 Feb 1.
With three clinically approved antibody-drug conjugates targeting HER2, this target is clearly identified to be of interest in oncology. Moreover, the advent of new bioconjugation technologies producing site-specific homogenous conjugates led to the opportunity of developing new medicines linking antibodies and payloads. Here, a new relevant HER2-targeting ADC was obtained by the conjugation of monomethyl auristatin E onto trastuzumab using McSAF Inside bioconjugation technology. The antibody-drug conjugate formed presented an average drug-to-antibody ratio of 4 with a high homogeneity and an excellent stability especially when incubated with human serum albumin or in human plasma. Moreover, it demonstrated a strong efficacy in an HER2 xenograft tumor model in mice, superior to the clinically approved antibody-drug conjugate ado-trastuzumab emtansine, with a complete tumor regression observed both macroscopically and microscopically demonstrating its therapeutic potential.
有三种针对 HER2 的临床批准的抗体药物偶联物，该靶点显然被认为是肿瘤学领域的研究重点。此外，新的生物偶联技术的出现，生产出了具有特定结合位点的均一偶联物，为连接抗体和有效载荷的新药开发提供了机会。在这里，通过 McSAF Inside 生物偶联技术，将单甲基澳瑞他汀 E 连接到曲妥珠单抗上，得到了一种新的相关 HER2 靶向 ADC。形成的抗体药物偶联物具有平均 4 的药物抗体比，具有很高的均一性和极好的稳定性，特别是在与人血清白蛋白或人血浆孵育时。此外，它在 HER2 异种移植肿瘤模型小鼠中表现出很强的疗效，优于临床批准的抗体药物偶联物 ado-trastuzumab emtansine，观察到完全的肿瘤消退，无论是宏观还是微观上都证明了其治疗潜力。
