Human Antibody Domains and Fragments Targeting Neutrophil Elastase as Candidate Therapeutics for Cancer and Inflammation-Related Diseases. Chu, X., Sun, Z., Baek, D., Li, W., Mellors, J. W., Shapiro, S. D., & Dimitrov, D. S. International Journal of Molecular Sciences, 22(20):11136, October, 2021. ![Human Antibody Domains and Fragments Targeting Neutrophil Elastase as Candidate Therapeutics for Cancer and Inflammation-Related Diseases [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Neutrophil elastase (NE) is a serine protease released during neutrophil maturation. High levels of NE are related to lung tissue damage and poor prognosis in cancer; thus, NE is a potential target for therapeutic immunotherapy for multiple lung diseases and cancers. Here, we isolate and characterize two high-affinity, specific, and noncompetitive anti-NE antibodies Fab 1C10 and VH 1D1.43 from two large phage-displayed human Fab and VH libraries. After fusion with human IgG1 Fc, both of them (VH-Fc 1D1.43 and IgG1 1C10) inhibit NE enzymatic activity with VH-Fc 1D1.43 showing comparable inhibitory effects to that of the small molecule NE inhibitor SPCK and IgG1 1C10 exhibiting even higher (2.6-fold) activity than SPCK. Their epitopes, as mapped by peptide arrays combined with structural modeling, indicate different mechanisms for blocking NE activity. Both VH-Fc and IgG1 antibodies block NE uptake by cancer cells and fibroblast differentiation. VH-Fc 1D1.43 and IgG1 1C10 are promising for the antibody-based immunotherapy of cancer and inflammatory diseases.
@article{chu_human_2021,
title = {Human {Antibody} {Domains} and {Fragments} {Targeting} {Neutrophil} {Elastase} as {Candidate} {Therapeutics} for {Cancer} and {Inflammation}-{Related} {Diseases}},
volume = {22},
issn = {1422-0067},
url = {https://www.mdpi.com/1422-0067/22/20/11136},
doi = {10.3390/ijms222011136},
abstract = {Neutrophil elastase (NE) is a serine protease released during neutrophil maturation. High levels of NE are related to lung tissue damage and poor prognosis in cancer; thus, NE is a potential target for therapeutic immunotherapy for multiple lung diseases and cancers. Here, we isolate and characterize two high-affinity, specific, and noncompetitive anti-NE antibodies Fab 1C10 and VH 1D1.43 from two large phage-displayed human Fab and VH libraries. After fusion with human IgG1 Fc, both of them (VH-Fc 1D1.43 and IgG1 1C10) inhibit NE enzymatic activity with VH-Fc 1D1.43 showing comparable inhibitory effects to that of the small molecule NE inhibitor SPCK and IgG1 1C10 exhibiting even higher (2.6-fold) activity than SPCK. Their epitopes, as mapped by peptide arrays combined with structural modeling, indicate different mechanisms for blocking NE activity. Both VH-Fc and IgG1 antibodies block NE uptake by cancer cells and fibroblast differentiation. VH-Fc 1D1.43 and IgG1 1C10 are promising for the antibody-based immunotherapy of cancer and inflammatory diseases.},
language = {eng},
number = {20},
journal = {International Journal of Molecular Sciences},
author = {Chu, Xiaojie and Sun, Zehua and Baek, Du-San and Li, Wei and Mellors, John W. and Shapiro, Steven D. and Dimitrov, Dimiter S.},
month = oct,
year = {2021},
pmid = {34681796},
keywords = {Application - Antibody Validation / Epitope Mapping, Application - Cancer Research, PEPperCHIP - Customized - Cyclic constrained, PEPperMAP - Epitope Mapping - Conformational},
pages = {11136},
}
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