Modulating Pseudomonas aeruginosa chronic Inflammation With The Anti-PcrV Antibody KB001: Results Of A Pilot Clinical and Pharmacodynamic Study In Subjects With Cystic Fibrosis

In vitro and in vivo properties of a fully human IgG1 monoclonal antibody that combats multidrug resistant Pseudomonas aeruginosa

“…It is axiomatic that mAbs are proven therapeutics for cancer and immunologic disorders (41), with increasing recognition that mAbs may serve as bona fide drugs for a variety of infectious diseases (42,43) including PA (19,20) by targeting surface-expressed virulence factors. We developed and expressed in CHO cells, a fully human mAb (LST-007) against the flagella of PA by targeting flagellin type b, one of the two major protein forms of this appendage.…”

“…Pre-clinically, a number of pharmacological studies have demonstrated the effectiveness of anti-PA virulence mAbs which have justified their clinical evaluation (16–18). For example, KB001 and panobacumab, human mAbs targeting PA virulence factors PcrV and 011 LPS serotype, respectively, have demonstrated positive clinical findings, albeit in a limited number of hospital-associated pneumonia and CF cases when added to standard-of-care treatment (19,20). These findings support passive immunization approaches targeting virulence factors especially since from an evolutionary point of view, they may be refractory to selection pressures due to their pivotal roles in bacterial infectivity and survival.…”

Novel approaches to the treatment ofPseudomonas aeruginosainfections in cystic fibrosis

“…These have ameliorated infection in a mouse pneumonia model with a subsequent reduction in mortality and bacterial load [ 104 ]. Preliminary reports of a phase I/II study in patients with CF suggested a dose-dependent reduction in sputum inflammatory markers although the full report is awaited [ 45 ] as are results from a phase I/II study of patients with ventilator associated pneumonia.…”