Pharmacokinetics and Safety Profile of the Human Anti-
            <i>Pseudomonas aeruginosa</i>
            Serotype O11 Immunoglobulin M Monoclonal Antibody KBPA-101 in Healthy Volunteers

Lazar, Hedvika; Horn, Michael P.; Zuercher, Adrian W.; Imboden, Martin A.; Durrer, Peter; Seiberling, Michael; Pokorny, Rolf; Hammer, Christophe; Lang, Aloïs B.

doi:10.1128/aac.01699-08

Cited by 43 publications

(28 citation statements)

References 17 publications

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“…KBPA101 was generated by immortalizing human B lymphocytes and selected for high effector function. KBPA101 demonstrated high specificity and efficacy in vitro and in vivo and was already tested in a clinical phase 1 study (23). Bacterial strains and clinical isolates.…”

mentioning

confidence: 99%

PreclinicalIn VitroandIn VivoCharacterization of the Fully Human Monoclonal IgM Antibody KBPA101 Specific forPseudomonas aeruginosaSerotype IATS-O11

Horn¹,

Zuercher²,

Imboden³

et al. 2010

Antimicrob Agents Chemother

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Pseudomonas aeruginosa infection in ventilator-associated pneumonia is a serious and often life-threatening complication in intensive care unit patients, and new treatment options are needed. We used B-cell-enriched peripheral blood lymphocytes from a volunteer immunized with a P. aeruginosa O-polysaccharide-toxin A conjugate vaccine to generate human hybridoma cell lines producing monoclonal antibodies specific for individual P. aeruginosa lipopolysaccharide serotypes. The fully human monoclonal antibody secreted by one of these lines, KBPA101, is an IgM/ antibody that binds P. aeruginosa of International Antigenic Typing System (IATS) serotype O11 with high avidity (5.81 ؋ 10 7 M ؊1 ؎ 2.8 ؋ 10 7 M ؊1 ) without cross-reacting with other serotypes. KBPA101 specifically opsonized the P. aeruginosa of IATS O11 serotype and mediated complement-dependent phagocytosis in vitro by the human monocyte-like cell line HL-60 at a very low concentration (half-maximal phagocytosis at 0.16 ng/ml). In vivo evaluation of KBPA101 demonstrated a dose-response relationship for protection against systemic infections in a murine burn wound sepsis model, where 70 to 100% of animals were protected against lethal challenges with P. aeruginosa at doses as low as 5 g/animal. Furthermore, a high efficacy of KBPA101 in protection from local respiratory infections in an acute lung infection model in mice was demonstrated. Preclinical toxicology evaluation on human tissue, in rabbits, and in mice did not indicate any toxicity of KBPA101. Based on these preclinical findings, the first human clinical trials have been initiated.

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confidence: 99%

PreclinicalIn VitroandIn VivoCharacterization of the Fully Human Monoclonal IgM Antibody KBPA101 Specific forPseudomonas aeruginosaSerotype IATS-O11

Horn¹,

Zuercher²,

Imboden³

et al. 2010

Antimicrob Agents Chemother

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“…In a multicenter, doubleblind study of Giamarellos et al (75) (76,77), monoclonal antibodies instead of focusing on bacterial clearance attainment. Example is the Panobacumab an IgM-type human monoclonal antibody that is directed against IATS 011 serotype P. aeruginosa, one of the most prevalent serotypes associated with nosocomial pneumonia (78). A multicenter Phase II study using panobacumab in combination with different antipseudomonal antibiotics in critical patients with HAP due to P. aeruginosa serotype O11, almost all with VAP, showed a good safety profile with good PKs (79).…”

Section: Macrolidesmentioning

confidence: 98%

Emerging drugs for nosocomial pneumonia

Liapikou

Torres

2016

Expert Opinion on Emerging Drugs

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“…In a phase I study in healthy volunteers, single ascending doses of panobacumab from 0.1 to 4 mg/kg were infused over 2 h. The drug was safe and well tolerated and no immunogenicity to panobacumab was detected. Panobacumab showed linear pharmacokinetics with a mean half-life between 70±24 and 95±20 hours [100].…”

Section: Pharmaceuticals)mentioning

confidence: 99%

Investigational drugs in phase I and phase II clincial trials for the treatment of hospital-acquired pneumonia

Falcó

Burgos

Papiol

et al. 2016

Expert Opinion on Investigational Drugs

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Pharmacokinetics and Safety Profile of the Human Anti- Pseudomonas aeruginosa Serotype O11 Immunoglobulin M Monoclonal Antibody KBPA-101 in Healthy Volunteers

Abstract: KBPA-101 is a human monoclonal antibody of the immunoglobulin M isotype, which is directed against the O-polysaccharide moiety of

Cited by 43 publications

References 17 publications

PreclinicalIn VitroandIn VivoCharacterization of the Fully Human Monoclonal IgM Antibody KBPA101 Specific forPseudomonas aeruginosaSerotype IATS-O11

PreclinicalIn VitroandIn VivoCharacterization of the Fully Human Monoclonal IgM Antibody KBPA101 Specific forPseudomonas aeruginosaSerotype IATS-O11

Emerging drugs for nosocomial pneumonia

Investigational drugs in phase I and phase II clincial trials for the treatment of hospital-acquired pneumonia

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