OBJECTIVES: To investigate the in vivo efficacy in a murine pulmonary infection model of panobacumab (KBPA101), a human IgM monoclonal antibody directed against the O-polysaccharide moiety of Pseudomonas aeruginosa serotype O11, and to describe the anti-inflammatory effects in the lung as a consequence of the treatment. METHODS: We established an experimental murine model of acute pneumonia by intranasal administration of P. aeruginosa serotype O11. Mice were treated, after infection, with a single intravenous injection of panobacumab and panobacumab lung bioavailability was assessed. Inflammatory parameters such as pro-inflammatory cytokine production and neutrophil recruitment in broncho-alveolar lavage fluid (BALF) were measured and bacterial load in the lung was analysed. RESULTS: Panobacumab plays a significant role in addition to the host innate immune response, leading to improved control of pulmonary infection. The IgM antibody is able to reach the broncho-alveolar space and reduce the pulmonary bacterial load as well as lung inflammation in a dose-dependent manner. Furthermore, panobacumab treatment leads to enhanced neutrophil recruitment in BALF while reducing the host-derived production of pro-inflammatory mediators and lung injury. CONCLUSIONS: These data provide evidence that panobacumab, an IgM-based immunotherapeutic, is highly efficacious in controlling acute lung infection by enhancing the natural innate immune response.
OBJECTIVES: To investigate the in vivo efficacy in a murinepulmonary infection model of panobacumab (KBPA101), a human IgM monoclonal antibody directed against the O-polysaccharide moiety of Pseudomonas aeruginosa serotype O11, and to describe the anti-inflammatory effects in the lung as a consequence of the treatment. METHODS: We established an experimental murine model of acute pneumonia by intranasal administration of P. aeruginosa serotype O11. Mice were treated, after infection, with a single intravenous injection of panobacumab and panobacumab lung bioavailability was assessed. Inflammatory parameters such as pro-inflammatory cytokine production and neutrophil recruitment in broncho-alveolar lavage fluid (BALF) were measured and bacterial load in the lung was analysed. RESULTS:Panobacumab plays a significant role in addition to the host innate immune response, leading to improved control of pulmonary infection. The IgM antibody is able to reach the broncho-alveolar space and reduce the pulmonary bacterial load as well as lung inflammation in a dose-dependent manner. Furthermore, panobacumab treatment leads to enhanced neutrophil recruitment in BALF while reducing the host-derived production of pro-inflammatory mediators and lung injury. CONCLUSIONS: These data provide evidence that panobacumab, an IgM-based immunotherapeutic, is highly efficacious in controlling acute lung infection by enhancing the natural innate immune response.
Authors: David M P De Oliveira; Brian M Forde; Timothy J Kidd; Patrick N A Harris; Mark A Schembri; Scott A Beatson; David L Paterson; Mark J Walker Journal: Clin Microbiol Rev Date: 2020-05-13 Impact factor: 26.132
Authors: Tania Cebrero-Cangueiro; Gema Labrador-Herrera; Marta Carretero-Ledesma; Soraya Herrera-Espejo; Rocío Álvarez-Marín; Jerónimo Pachón; José Miguel Cisneros; María Eugenia Pachón-Ibáñez Journal: Life Sci Alliance Date: 2022-06-21
Authors: Evelyn De Tavernier; Laurent Detalle; Erika Morizzo; Annelies Roobrouck; Severine De Taeye; Melanie Rieger; Tom Verhaeghe; Andreia Correia; Rob Van Hegelsom; Rita Figueirido; Jeroen Noens; Søren Steffensen; Thomas Stöhr; Willem Van de Velde; Erik Depla; Bruno Dombrecht Journal: J Biol Chem Date: 2016-05-20 Impact factor: 5.157