Abstract：
:Harnessing complement-mediated cytotoxicity by therapeutic antibodies has been limited because of dependency on size and density of antigen, structural constraints resulting from orientation of antibody binding, and blockade of complement activation by inhibitors expressed on target cells. We developed a modular bispecific antibody platform that directs the complement-initiating protein C1q to target cells, increases local complement deposition and induces cytotoxicity against target antigens with a wide-range of expression. The broad utility of this approach to eliminate both prokaryotic and eukaryotic cells was demonstrated by pairing a unique C1q-recruiting arm with multiple targeting arms specific for Staphylococcus aureus, Pseudomonas aeruginosa, B-cells and T-cells, indicating applicability for diverse indications ranging from infectious diseases to cancer. Generation of C1q humanized mice allowed for demonstration of the efficacy of this approach to clear disease-inducing cells in vivo. In summary, we present a novel, broadly applicable, and versatile therapeutic modality for targeted cell depletion.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Cruz JW,Damko E,Modi B,Tu N,Meagher K,Voronina V,Gartner H,Ehrlich G,Rafique A,Babb R,Aneja P,Potocky TB,D' Orvilliers A,Coppi A,E SY,Qiu H,Williams CM,Bennett BL,Chen G,Macdonald L,Olson W,Lin JC,Stahl N,Mudoi
10.1038/s41598-019-48461-1subject
Has Abstractpub_date
2019-08-19 00:00:00pages
12031issue
1issn
2045-2322pii
10.1038/s41598-019-48461-1journal_volume
9pub_type
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Scientific reports
pub_type： 杂志文章
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pub_type： 已发布勘误
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