Antibody-drug conjugates with high drug loading

The present invention provides transglutaminase-mediated antibody-drug conjugates with high antibody-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates. 本发明提供了具有高药物-抗体比例(DAR)的转谷氨酰胺酶-介导的抗体-药物缀合物，其包含：1)含谷氨酰胺的标签、内源谷氨酰胺，和/或通过抗体工程化或工程化的转谷氨酰胺酶(例如，具有改变的底物特异性)而成为反应性的内源谷氨酰胺；和2)包括胺供体单元、接头和试剂部分的胺供体试剂，其中所述DAR是至少约5。本发明还提供了这种较高药物负载的抗体-药物缀合物的制备方法和使用方法。