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

International Journal of Molecular Medicine

Volumn 30, Issue 3, 2012, Pages 455-464

  Adawi, Azmi ^a   Bisignano, Carlo ^b   Genovese, Tiziana ^c   Filocamo, Angela ^b   Khouri Assi, Camellia ^d   Neville, Anat ^e   Feuerstein, Giora Z ^f   Cuzzocrea, Salvatore ^c   Neville, Lewis F ^a  

^a Lostam BioPharmaceuticals Ltd   (Israel)

^b UNIVERSITY OF MESSINA   (Italy)

^c UNIVERSITY OF MESSINA   (Italy)

^d Ilan University   (Israel)

^e BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^f Farmacon Consulting   (United States)

Author keywords

Flagellin; Monoclonal antibody; Multidrug resistance; Passive immunization; Pseudomonas aeruginosa

Indexed keywords

AMIKACIN; ANTIBIOTIC AGENT; COLISTIN; FLAGELLIN; GENTAMICIN; IMIPENEM; IMMUNOGLOBULIN G1 ANTIBODY; LST 007; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG;

AFFINITY CHROMATOGRAPHY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC SENSITIVITY; AREA UNDER THE CURVE; ARTICLE; BACTERIAL STRAIN; BINDING KINETICS; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; IN VITRO STUDY; IN VIVO STUDY; ISOELECTRIC FOCUSING; MAXIMUM PLASMA CONCENTRATION; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; PNEUMONIA; PRIORITY JOURNAL; PROTECTION; PROTEIN EXPRESSION; PROTEIN TARGETING; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTION; SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTIBODIES, MONOCLONAL; BRONCHOALVEOLAR LAVAGE FLUID; CHO CELLS; CRICETINAE; DRUG RESISTANCE, MULTIPLE, BACTERIAL; FLAGELLIN; HUMANS; IMMUNOGLOBULIN G; MICE; PNEUMONIA; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS; RECOMBINANT PROTEINS;

EID: 84865169311     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm.2012.1040     Document Type: Article

References (54)

1. Boucher HW, Talbot GH, Bradley JS, et al: Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48: 1-12, 2009.
2. ECDC/EMEA Joint Technical Report. The Bacterial Challenge: Time to React. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. pp1-42, 2009. EMEA doc. ref. EMEA/576176/2009 Stockholm, September 2009. doi 10.2900/2518.
3. Driscoll JA, Brody SL and Kollef MH: The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections. Drugs 67: 351-368, 2007. (Pubitemid 46425550)
4. Levin AS and Oliveira MS: The challenge of multidrug resistance: the treatment of gram-negative rod infections. Shock 30: 30-33, 2008.
5. Fujitani S, Sun HY, Yu VL and Weingarten JA: Pneumonia due to Pseudomonas aeruginosa: part I: epidemiology, clinical diagnosis, and source. Chest 139: 909-919, 2011.
6. Pallett A and Hand K: Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria. J Antimicrob Chemother 65: S25-S33, 2010.
7. Flume PA, O'Sullivan BP, Robinson KA, et al: Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med 176: 957-969, 2007. (Pubitemid 350127838)
8. Cohen-Cymberknoh M, Shoseyov D and Kerem E: Managing cystic fibrosis: strategies that increase life expectancy and improve quality of life. Am J Respir Crit Care Med 183: 1463-1471, 2011.
9. Hoiby N: Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis. BMC Med 9: 32, 2011.
10. Stover CK, Pham XQ, Erwin AL, et al: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406: 959-964, 2000.
11. Dean CR, Visalli MA, Projan SJ, Sum PE and Bradford PA: Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 47: 972-978, 2003. (Pubitemid 36254223)
12. Chastre J and Fagon JY: Ventilator-associated pneumonia. Am J Resp Crit Care Med 165: 867-903, 2002. (Pubitemid 34774654)
13. Cegelski L, Marshall GR, Eldridge GR and Hultgren SJ: The biology and future prospects of antivirulence therapies. Nature Rev Microbiol 6: 17-27, 2008. (Pubitemid 350286217)
14. Chartrain M and Chu L: Development and production of commercial therapeutic monoclonal antibodies in mammalian cell expression systems: an overview of the current upstream methodologies. Curr Pharm Biotechnol 9: 447-467 2008.
15. De Jesus M and Wurm FM: Manufacturing recombinant proteins in kg-ton quantities using animal cells in bioreactors. Eur J Pharm Biopharm 78: 184-188, 2011.
16. Baer M, Sawa T, Flynn P, et al: An engineered human antibody fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent antibacterial activity. Infect Immun 77: 1083-1090, 2009.
17. Secher T, Fauconnier L, Szade A, et al: Anti-Pseudomonas aeruginosa serotype O11 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection. J Antimicrob Chemother 66: 1100-1109, 2011.
18. Horn MP, Zuercher AW, Imboden MA, et al: Preclinical in vitro and in vivo characterization of the fully human monoclonal IgM antibody KBPA101 specific for Pseudomonas aeruginosa serotype IATS-O11. Antimicrob Agents Chemother 54: 2338-2344, 2010.
19. Lu Q, Rouby JJ, Laterre PF, et al: Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia. J Antimicrob Chemother 66: 1110-1116, 2011.
20. Milla CE, Accurso FJ, Chmiel J, et al: Modulating Pseudomonas aeruginosa chronic inflammation with the anti-PcrV antibody KB001: Results of a pilot clinical and pharmacodynamic study in subjects with cystic fibrosis. Am J Respir Crit Care Med 181: A1845, 2010.
21. Samatey FA, Imada K, Nagashima S, et al: Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling. Nature 410: 331-337, 2001. (Pubitemid 32246042)
22. Yonekura K, Maki-Yonekura S and Namba K: Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature 424: 643-650, 2003. (Pubitemid 36987983)
23. Smith KD, Andersen-Nissen E, Hayashi F, et al: Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat Immunol 4: 1247-1253, 2003. (Pubitemid 37540694)
24. Ansorg RA, Knoche ME, Spies AF and Kraus CJ: Differentiation of the major flagellar antigens of Pseudomonas aeruginosa by the slide coagglutination technique. J Clin Microbiol 20: 84-88, 1984. (Pubitemid 14077731)
25. Montie TJ and Anderson TR: Enzyme-linked immunosorbent assay for detection of Pseudomonas aeruginosa H (flagellar) antigen. Eur J Clin Microbiol Infect Dis 7: 256-260, 1988.
26. Morgan JA, Bellingham NF, Winstanley C, Ousley MA, Hart CA and Saunders JR: Comparison of flagellin genes from clinical and environmental Pseudomonas aeruginosa isolates. Appl Environ Microbiol 65: 1175-1179, 1999.
27. Rosok MJ, Stebbins MR, Connelly K, Lostrom ME and Siadak AW: Generation and characterization of murine anti flagellum monoclonal antibodies that are protective against lethal challenge with Pseudomonas aeruginosa. Infect Immun 58: 3819-3828, 1990.
28. Ochi H, Ohtsuka H, Yokota S, et al: Inhibitory activity on bacterial motility and in vivo protective activity of human monoclonal antibodies against flagella of Pseudomonas aeruginosa. Infect Immun 59: 550-554, 1991.
29. Landsperger WJ, Kelly-Wintenberg KD, Montie TC, et al: Inhibition of bacterial motility with human antiflagellar monoclonal antibodies attenuates Pseudomonas aeruginosa-induced pneumonia in the immunocompetent rat. Infect Immun 62: 4825-4830, 1994. (Pubitemid 24332782)
30. Neville LF, Barnea Y, Hammer-Munz O, et al: Antibodies raised against N′-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection. Int J Mol Med 16: 165-171, 2005.
31. Barnea Y, Carmeli Y, Neville LF, et al: Therapy with anti-flagellin A monoclonal antibody limits Pseudomonas aeruginosa invasiveness in a mouse burn wound sepsis model. Burns 35: 390-396, 2009.
32. Eren R, Landstein D, Terkieltaub D, et al: Preclinical evaluation of two neutralizing human monoclonal antibodies against hepatitis C virus (HCV): a potential treatment to prevent HCV reinfection in liver transplant patients. J Virol 80: 2654-2664, 2006. (Pubitemid 43346361)
33. Neuhoff V, Arold N, Taube D and Ehrhardt W: Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250. Electrophoresis 9: 255-262, 1988.
34. Rashid MH and Kornberg A: Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 97: 4885-4890, 2000. (Pubitemid 30238652)
35. Boswell CA, Tesar DB, Mukhyala K, Theil FP, Fielder PJ and Khawli LA: Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug Chem 21: 2153-2163, 2010.
36. -/- mice. MAbs 2: 571-575, 2010.
37. Freire-Moran L, Aronsson B, Manz C, et al: Critical shortage of new antibiotics in development against multidrug-resistant bacteria - time to react is now. Drug Resist Updat 14: 118-124, 2011.
38. Page MG and Heim J: Prospects for the next anti-Pseudomonas drug. Curr Opin Pharmacol 9: 558-565, 2009.
39. Talbot GH: What is in the pipeline for Gram-negative pathogens? Expert Rev Anti Infect Ther 6: 39-49, 2008.
40. Mouton JW, Ambrose PG, Canton R et al: Conserving antibiotics for the future: New ways to use old and new drugs from a pharmacokinetic and pharmacodynamic perspective. Drug Resist Updat 14: 107-117, 2011.
41. Reichert JM: Monoclonal antibodies as innovative therapeutics. Curr Pharm Biotechnol 9: 423-430, 2008.
42. Lowy I, Molrine DC, Leav BA, et al: Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 362: 197-205, 2010.
43. Lopez EL, Contrini MM, Glatstein E, et al: Safety and pharmacokinetics of urtoxazumab, a humanized monoclonal antibody, against Shiga-like toxin 2 in healthy adults and in pediatric patients infected with Shiga-like toxin-producing Escherichia coli. Antimicrob Agents Chemother 54: 239-243, 2010.
44. Verma A, Schirm M, Arora SK, Thibault P, Logan SM and Ramphal R: Glycosylation of b-type flagellin of Pseudomonas aeruginosa: structural and genetic basis. J Bacteriol 188: 4395-4403, 2006. (Pubitemid 43865759)
45. Shanks KK, Guang W, Kim KC and Lillehoj EP: Interleukin-8 production by human airway epithelial cells in response to Pseudomonas aeruginosa clinical isolates expressing type a or type b flagellins. Clin Vaccine Immunol 17: 1196-1202, 2010.
46. Bannister D, Popovic B, Sridharan S, et al: Epitope mapping and key amino acid identification of anti-CD22 immunotoxin CAT-8015 using hybrid β-lactamase display. Protein Eng Des Sel 24: 351-360, 2011.
47. Bone RC: Monoclonal antibodies to endotoxin. New allies against sepsis? JAMA 266: 1125-1126, 1991.
48. Bone RC: Why sepsis trials fail. JAMA 276: 565-566, 1996.
49. Holmes D: Buy buy bispecific antibodies. Nat Rev Drug Discov 10: 798-800, 2011.
50. Gewirtz AT, Vijay-Kumar M, Brant SR, Duerr RH, Nicolae DL and Cho JH: Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease. Am J Physiol Gastrointest Liver Physiol 290: G1157-G1163, 2006. (Pubitemid 43788297)
51. Blohmke CJ, Park J, Hirschfeld AF, et al: TLR5 as an anti-inflammatory target and modifier gene in cystic fibrosis. J Immunol 185: 7731-7738, 2010.
52. Hawn TR, Wu H, Grossman JM, Hahn BH, Tsao BP and Aderem A: A stop codon polymorphism of Toll-like receptor 5 is associated with resistance to systemic lupus erythematosus. Proc Natl Acad Sci USA 102: 10593-10597, 2005. (Pubitemid 41061599)
53. Nilsson E, Larsson A, Olesen HV, Wejaker PE and Kollberg H: Good effect of IgY against Pseudomonas aeruginosa infections in cystic fibrosis patients. Pediatr Pulmonol 43: 892-899, 2008.
54. Nilsson E, Amini A, Wretlind B and Larsson A: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin. J Chromatogr B Analyt Technol Biomed Life Sci: 856: 75-80, 2007. (Pubitemid 47302902)