Anti-Pseudomonas aeruginosa serotype O11 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection.

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.

Delineation of human cord blood hematopoietic progenitor cell subsets with a unique monoclonal antibody AY19.

AY19, a unique mAb was used to better characterize the umbilical cord blood hematopoietic progenitor subpopulations. This mAb identifies an 85 kDa cell surface glycoprotein. In this present study we showed that AY19 mAb is reactive with 50-60% of the CD34+ cord blood cells. Extensive phenotypical studies revealed that AY19 mAb defines a novel CD34+ subset different from the ones defined by anti-CD90, anti-CD38, anti-CD33, anti-CD71, anti-CD19, anti-CD7 or anti-HLA-DR mAbs. We show that AY19 mAb reacts with both primitive and committed progenitors including myeloid and lymphoid progenitors. In addition, sorted CD34+high/AY19+ cells contain an increased number of CFU-GM and a decreased number of BFU-E compared with sorted CD34+high/AY19- cells. We show that AY19 mAb exhibits agonistic properties by inducing a significant increase in the size of CFU-GM colonies when added to serum-free liquid cultures of hematopoietic progenitors. This suggests that AY19 mAb identifies a cell surface receptor which may be involved in the regulation of hematopoietic cell proliferation.