Qasba Pradman K
Center for Cancer Research, National Cancer Institute, National Institutes of Health , Frederick, Maryland 21702-1201, United States.
Bioconjug Chem. 2015 Nov 18;26(11):2170-5. doi: 10.1021/acs.bioconjchem.5b00173. Epub 2015 Jun 23.
The therapeutic cargo molecules conjugated to a specific site on a monoclonal antibody (mAb), called antibody-drug conjugates (ADCs), are becoming powerful tools in cancer treatment. Generally, the cargo molecules conjugate at the cysteine or lysine residue of the mAb, which generally results in a highly heterogeneous ADC. Therapeutic cargo molecules need to be conjugated in a site-specific manner to the mAb so that the bioefficacy of these molecules is not compromised. The mAb (IgG1) are N-glycosylated at the conserved residue Asn(297), which is present in each heavy chain of the IgG1, near the CH2 domain of the Fc fragment. The mutant or wild-type glycosyltransferases transfer sugars with a chemical handle to the glycan molecule of IgG1, making the site-specific linking of cargo molecules possible via the chemical handle, and thus making the process an invaluable technique for the production of homogeneous ADCs.
与单克隆抗体（mAb）特定位点偶联的治疗性载药分子，即抗体药物偶联物（ADC），正成为癌症治疗中的有力工具。一般来说，载药分子在mAb的半胱氨酸或赖氨酸残基处偶联，这通常会导致ADC高度异质性。治疗性载药分子需要以位点特异性方式与mAb偶联，这样这些分子的生物功效才不会受到损害。mAb（IgG1）在保守残基Asn（297）处进行N-糖基化，该残基存在于IgG1的每条重链中，靠近Fc片段的CH2结构域。突变型或野生型糖基转移酶将带有化学手柄的糖转移到IgG1的聚糖分子上，使得载药分子能够通过化学手柄进行位点特异性连接，从而使该过程成为生产均质ADC的一项宝贵技术。
