Radiolabeled antibodies to Bacillus anthracis toxins are bactericidal and partially therapeutic in experimental murine anthrax.
Bacillus anthracis is a powerful agent for use in biological warfare, and infection with the organism is associated with a high rate of mortality, underscoring the need for additional effective therapies for anthrax. Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver a microbicidal radioactive nuclide to a site of infection. RIT has proven therapeutic in experimental models of viral, bacterial, and fungal infections; but it is not known whether this approach can successfully employ toxin binding monoclonal antibodies (MAbs) for diseases caused by toxigenic bacteria. Indirect immunofluorescence studies with MAbs to protective antigen (MAbs 7.5G gamma2b and 10F4 gamma1) and lethal factor (MAb 14FA gamma2b) revealed the surface expression of toxins on bacterial cells. Scatchard analysis of MAbs revealed high binding constants and numerous binding sites on the bacterial surface. To investigate the microbicidal properties of these MAbs, our group radiolabeled MAbs with either (188)Re or (213)Bi. In vitro, (213)Bi was more efficient than (188)Re in mediating microbicidal activity against B. anthracis. The administration of MAbs [(213)Bi]10F4 gamma1 and [(213)Bi]14FA gamma2b prolonged the survival of A/JCr mice infected with B. anthracis Sterne bacterial cells but not B. anthracis Sterne spores. These results indicate that RIT with MAbs that target B. anthracis toxin components can be used to treat experimental anthrax infection and suggest that toxigenic bacteria may be targeted with radiolabeled MAbs.
Rivera
Johanna
J
Department of Microbiology and Immunology, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Nakouzi
Antonio S
AS
Morgenstern
Alfred
A
Bruchertseifer
Frank
F
Dadachova
Ekaterina
E
Casadevall
Arturo
A
D000818:Animals; D000881:Anthrax / Q000532:radiotherapy*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000528:radiation effects*; D001427:Bacterial Toxins / Q000276:immunology*; D001729:Bismuth / Q000627:therapeutic use; D002460:Cell Line; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D016253:Microscopy, Immunoelectron; D016499:Radioimmunotherapy
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D001729:Bismuth
Cancer Drug Deliv. 1985 Summer;2(3):171-2
4052930
Cancer Biother Radiopharm. 2004 Apr;19(2):135-47
15186593
Infect Immun. 2006 Jul;74(7):4149-56
16790789
Expert Rev Mol Med. 2006 Apr 11;8(7):1-18
16608555
Antimicrob Agents Chemother. 2004 Mar;48(3):1004-6
14982795
Cell Microbiol. 2003 Jan;5(1):15-23
12542467
PLoS Med. 2006 Nov;3(11):e427
17090209
Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:189-98
6328915
Proc Natl Acad Sci U S A. 1982 May;79(10):3162-6
6285339
Microb Pathog. 2005 May-Jun;38(5-6):209-25
15925272
Annu Rev Microbiol. 2001;55:647-71
11544370
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10942-7
12930899
J Nucl Med. 2005 Jan;46 Suppl 1:115S-27S
15653660
Expert Opin Drug Deliv. 2005 Nov;2(6):1075-84
16296810
J Biol Chem. 2009 Sep 11;284(37):25077-86
19617628
Antimicrob Agents Chemother. 2004 May;48(5):1624-9
15105113
J Immunol. 2006 May 15;176(10):6076-84
16670316
Annu Rev Cell Dev Biol. 2003;19:45-70
14570563
Nat Rev Drug Discov. 2004 Jun;3(6):488-99
15173838
J Nucl Med. 2004 Feb;45(2):313-20
14960655
Anal Chem. 2005 Oct 1;77(19):6288-91
16194090
J Infect Dis. 2006 May 15;193(10):1427-36
16619191