Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

doi:10.3390/molecules23061326

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	Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy
	Zhou, Dapeng 2; Xu, Lan 3; Huang, Wei 1,4; Tonn, Torsten 5,6
刊名	MOLECULES
	2018-06
卷号	23 期号:6
关键词	MUC1 tandem repeat antibodies glycopeptide co-crystal
ISSN号	1420-3049
DOI	10.3390/molecules23061326
文献子类	Review
英文摘要	Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.
资助项目	National Natural Science Foundation of China[81570007] ; National Key Research and Development Plan[2017YFA0505901]
WOS关键词	CHIMERIC ANTIGEN RECEPTOR ; SIALYL-TN-ANTIGENS ; MHC CLASS-I ; ANTI-MUC1 MONOCLONAL-ANTIBODY ; SYNTHETIC ANTITUMOR VACCINES ; HUMAN-IMMUNOGLOBULIN HEAVY ; EPITHELIAL OVARIAN-CANCER ; ADVANCED BREAST-CANCER ; TUMOR-ASSOCIATED MUC1 ; O-GLYCOSYLATION
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000435875400088
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279721]
专题	生物技术药物研发中心（筹）药物安全性评价中心
通讯作者	Zhou, Dapeng; Xu, Lan
作者单位	1.ShanghaiTech Univ, IHuman Inst, Shanghai 201203, Peoples R China; 2.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China; 3.ShanghaiTech Univ, Lab Antibody Struct, Shanghai Inst Adv Immunochem Studies, Shanghai 201203, Peoples R China; 4.ShanghaiTech Univ, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Chinese Acad Sci, Shanghai 201203, Peoples R China; 5.German Red Cross Blood Donat Serv North East, Inst Transfus Med Dresden, D-01307 Dresden, Germany; 6.Carl Gustav Carus Tech Univ, Fac Med, D-01307 Dresden, Germany
推荐引用方式 GB/T 7714	Zhou, Dapeng,Xu, Lan,Huang, Wei,et al. Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy[J]. MOLECULES,2018,23(6).
APA	Zhou, Dapeng,Xu, Lan,Huang, Wei,&Tonn, Torsten.(2018).Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy.MOLECULES,23(6).
MLA	Zhou, Dapeng,et al."Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy".MOLECULES 23.6(2018).