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

Adawi,Azmi; Bisignano,Carlo; Genovese,Tiziana; Filocamo,Angela; Khouri-Assi,Camellia; Neville,Anat; Feuerstein,Giora  Z.; Cuzzocrea,Salvatore; Neville,Lewis  F.

doi:10.3892/ijmm.2012.1040

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

Authors:
- Azmi Adawi
- Carlo Bisignano
- Tiziana Genovese
- Angela Filocamo
- Camellia Khouri-Assi
- Anat Neville
- Giora Z. Feuerstein
- Salvatore Cuzzocrea
- Lewis F. Neville
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Affiliations: Lostam BioPharmaceuticals, Nazareth, Israel, Department of Pharmacobiology, School of Pharmacy, University of Messina, Messina, Italy, Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy, St. Vincent Hospital, Nazareth, Israel, Department of Family Medicine, Ben-Gurion University of the Negev, Beer-Sheva, Israel, Farmacon Consulting, Bryn Mawr, PA, USA
Published online on: June 20, 2012 https://doi.org/10.3892/ijmm.2012.1040
Pages: 455-464
Copyright: © Adawi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The development of an anti-bacterial drug in the form of a monoclonal antibody (mAb) targeting an exposed virulence factor, represents an innovative therapeutic strategy. Consequently, a fully human IgG1 mAb (LST-007) targeting Pseudomonas aeruginosa (PA) flagellin type b was recombinantly expressed and characterized in vitro and in an infection model driven by a multidrug resistant (MDR) PA strain. LST-007 demonstrated a highly specific binding towards whole PA bacteria harboring flagellin type b and its recombinant counterpart, with a KD of 7.4x10-10 M. In bioactivity assays, LST-007 or titers of Cmax sera derived from pharmacokinetic studies, markedly attenuated PA motility in an equipotent manner. In vivo, parenteral LST-007 (20 mg/kg) given as a single or double-dosing paradigm post-infection, afforded survival (up to 75% at Day 7) in a lethal model of pneumonia driven by the intratracheal (i.t.) instillation of an LD80 of the MDR PA isolate. This protective effect was markedly superior to that of imipenem (30% survival at Day 7) and totally devoid with an irrelevant, human isotype mAb. These data lay credence that LST-007 may be a valuable adjunct to the limited list of anti-bacterials that can tackle MDR PA strains, thereby warranting its continued development for eventual clinical evaluation.

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