{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T21:22:48Z","timestamp":1793136168742,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008593","name":"European Respiratory Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"European Respiratory Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pseudomonas aeruginosainfection is associated with worse outcomes in bronchiectasis. Impaired neutrophil antimicrobial responses contribute to bacterial persistence. Gremubamab is a bivalent, bispecific monoclonal antibody targeting Psl exopolysaccharide and the type 3 secretion system component PcrV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study evaluated the efficacy of gremubamab to enhance killing of P. aeruginosaby neutrophils from patients with bronchiectasis and to prevent P. aeruginosa\u2013associated cytotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>P. aeruginosaisolates from a global bronchiectasis cohort (n\u2009=\u2009100) underwent whole-genome sequencing to determine target prevalence. Functional activity of gremubamab against selected isolates was tested in vitroand in vivo. Patients with bronchiectasis (n\u2009=\u200911) and control subjects (n\u2009=\u200910) were enrolled, and the effect of gremubamab in peripheral blood neutrophil opsonophagocytic killing (OPK) assays against P. aeruginosawas evaluated. Serum antibody titers to Psl and PcrV were determined (n\u2009=\u200930; 19 chronic P. aeruginosainfection, 11 no known P. aeruginosainfection), as was the effect of gremubamab treatment in OPK and anti\u2013cytotoxic activity assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Psl and PcrV were conserved in isolates from chronically infected patients with bronchiectasis. Seventy-three of 100 isolates had a full psllocus, and 99 of 100 contained the pcrVgene, with 20 distinct full-length PcrV protein subtypes identified. PcrV subtypes were successfully bound by gremubamab and the monoclonal antibody\u2013mediated potent protective activity against tested isolates. Gremubamab increased bronchiectasis patient neutrophil-mediated OPK (+34.6\u2009\u00b1\u20098.1%) and phagocytosis (+70.0\u2009\u00b1\u200948.8%), similar to effects observed in neutrophils from control subjects (OPK, +30.1\u2009\u00b1\u20097.6%). No evidence of competition between gremubamab and endogenous antibodies was found, with protection against P. aeruginosa\u2013induced cytotoxicity and enhanced OPK demonstrated with and without addition of patient serum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gremubamab enhanced bronchiectasis patient neutrophil phagocytosis and killing of P. aeruginosaand reduced virulence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202308-1403oc","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T17:05:36Z","timestamp":1715879136000},"page":"35-46","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":34,"title":["A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Neutrophil-Mediated Killing of\n                    <i>Pseudomonas aeruginosa<\/i>\n                    in Patients with Bronchiectasis"],"prefix":"10.1093","volume":"210","author":[{"given":"Merete B.","family":"Long","sequence":"first","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Gilmour","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Kehl","sequence":"additional","affiliation":[{"name":"Vaccine and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Tabor","sequence":"additional","affiliation":[{"name":"Vaccine and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, 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