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Here we present a novel, bifunctional immunotherapy (CTX-09) with the ability to harness endogenous anti-galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl-glucosamine (anti-\u03b1Gal) antibodies to drive immune-mediated clearance of Gram-negative bacteria. In addition, CTX-09 has direct-acting broad-spectrum bactericidal activity equivalent to colistin and meropenem against 1952 Gram-negative clinical isolates. In vitro, CTX-09 demonstrated immune-mediated efficacy through recruitment of anti-\u03b1Gal antibodies and engagement of antibody effector mechanisms that enhanced bacterial clearance at sub-bactericidal concentrations. In vivo, at sub-bactericidal doses, CTX-09 demonstrated anti-\u03b1Gal antibody driven clearance of susceptible and multidrug-resistant (MDR) strains. In the presence of anti-\u03b1Gal antibody, bacterial burden was reduced by &amp;gt;99.9% (3-log10) in neutropenic mouse thigh and pneumonia infection models. This data suggest that CTX-09 or other antibody-recruiting molecules have potential to address the urgent clinical need of patients with gram-negative infections using a novel immunotherapeutic mechanism.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf055","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T17:56:50Z","timestamp":1746813410000},"page":"1617-1629","source":"Crossref","is-referenced-by-count":2,"title":["Harnessing endogenous anti-glycan antibodies using a novel, bifunctional immunotherapy to treat gram-negative bacterial infections"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4444-780X","authenticated-orcid":false,"given":"Bailey","family":"Hairsine","sequence":"first","affiliation":[{"name":"Centauri Therapeutics Limited , Cheshire,","place":["United 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