{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T15:29:33Z","timestamp":1777130973108,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phosphorylcholine (PC) is an important pro\u2010inflammatory damage\u2010associated molecular pattern. Previous data have shown that natural IgM anti\u2010PC protects against cardiovascular disease. We aimed to develop a monoclonal PC IgG antibody with anti\u2010inflammatory and anti\u2010atherosclerotic properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using various techniques PC antibodies were validated and optimized. In vivo testing was performed in a femoral artery cuff model in ApoE3*Leiden mice. Safety studies are performed in rats and cynomolgus monkeys.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A chimeric anti\u2010PC (PC\u2010mAb(T15), consisting of a human IgG1 Fc and a mouse T15\/E06 Fab) was produced, and this was shown to bind specifically to epitopes in human atherosclerotic tissues. The cuff model results in rapid induction of inflammatory genes and altered expression of genes associated with ER stress and choline metabolism in the lesions. Treatment with PC\u2010mAb(T15) reduced accelerated atherosclerosis via reduced expression of endoplasmic reticulum stress markers and CCL2 production. Recombinant anti\u2010PC Fab fragments were identified by phage display and cloned into fully human IgG1 backbones creating a human monoclonal IgG1 anti\u2010PC (PC\u2010mAbs) that specifically bind PC, apoptotic cells and oxLDL. Based on preventing macrophage oxLDL uptake and CCL2 production, four monoclonal PC\u2010mAbs were selected, which to various extent reduced vascular inflammation and lesion development. Additional optimization and validation of two PC\u2010mAb antibodies resulted in selection of PC\u2010mAb X19\u2010A05, which inhibited accelerated atherosclerosis. Clinical grade production of this antibody (ATH3G10) significantly attenuated vascular inflammation and accelerated atherosclerosis and was tolerated in safety studies in rats and cynomolgus monkeys.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chimeric anti\u2010PCs can prevent accelerated atherosclerosis by inhibiting vascular inflammation directly and through reduced macrophage oxLDL uptake resulting in decreased lesions. PC\u2010mAb represents a novel strategy for cardiovascular disease prevention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13234","type":"journal-article","created":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T16:20:45Z","timestamp":1608481245000},"page":"141-156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3648-9130","authenticated-orcid":false,"given":"M. R.","family":"de Vries","sequence":"first","affiliation":[{"name":"From the Deptartment of Surgery LUMC Leiden The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine LUMC Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. M.","family":"Ewing","sequence":"additional","affiliation":[{"name":"From the Deptartment of Surgery LUMC Leiden The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine LUMC Leiden The Netherlands"},{"name":"Deptartment of Cardiology LUMC Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. C. M.","family":"de Jong","sequence":"additional","affiliation":[{"name":"From the Deptartment of Surgery LUMC Leiden The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine LUMC Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. R.","family":"MacArthur","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism Harvard T.H. Chan School of Public Health Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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P.","family":"Karabina","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 933 H\u00f4pital Armand\u2010Trousseau Sorbonne Universit\u00e9 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Sexton","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceutical Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Dahlbom","sequence":"additional","affiliation":[{"name":"Dept. of Medicine Karolinska University Hospital Huddinge and Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Bergman","sequence":"additional","affiliation":[{"name":"Athera Biotechnologies Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. R.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism Harvard T.H. 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