A Versatile Chemo-Enzymatic Conjugation Approach Yields Homogeneous and Highly Potent Antibody-Drug Conjugates
AbstractThe therapeutic efficacy of antibodies can be successfully improved through targeted delivery of potent cytotoxic drugs in the form of antibody-drug conjugates. However, conventional conjugation strategies lead to heterogeneous conjugates with undefined stoichiometry and sites, even with considerable batch-to-batch variability. In this study, we have developed a chemo-enzymatic strategy by equipping the C-terminus of anti-CD20 ofatumumab with a click handle using Sortase A, followed by ligation of the payload based on a strain-promoted azide-alkyne cycloaddition to produce homogeneous conjugates. The resulting antibody-drug conjugates fully retained their antigen binding capability and proved to be internalized and trafficked to the lysosome, which released the payload with a favorable efficacy in vitro and in vivo. Thus, this reported method is a versatile tool with maximum flexibility for development of antibody-drug conjugates and protein modification. View Full-Text
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Xu, Y.; Jin, S.; Zhao, W.; Liu, W.; Ding, D.; Zhou, J.; Chen, S. A Versatile Chemo-Enzymatic Conjugation Approach Yields Homogeneous and Highly Potent Antibody-Drug Conjugates. Int. J. Mol. Sci. 2017, 18, 2284.
Xu Y, Jin S, Zhao W, Liu W, Ding D, Zhou J, Chen S. A Versatile Chemo-Enzymatic Conjugation Approach Yields Homogeneous and Highly Potent Antibody-Drug Conjugates. International Journal of Molecular Sciences. 2017; 18(11):2284.Chicago/Turabian Style
Xu, Ying; Jin, Shijie; Zhao, Wenbin; Liu, Wenhui; Ding, Ding; Zhou, Jie; Chen, Shuqing. 2017. "A Versatile Chemo-Enzymatic Conjugation Approach Yields Homogeneous and Highly Potent Antibody-Drug Conjugates." Int. J. Mol. Sci. 18, no. 11: 2284.
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