1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Radiolabeled Antibodies for Therapy of Infectious Diseases

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • PDF
    381.07 Kb
  • HTML
    68.56 Kb
  • XML
    57.45 Kb
  • Authors: Ekaterina Dadachova1, Arturo Casadevall3
  • Editors: James E. Crowe Jr.5, Diana Boraschi6, Rino Rappuoli7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Radiology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461; 2: Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461; 3: Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461; 4: Department of Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461; 5: Vanderbilt University School of Medicine, Nashville, TN; 6: National Research Council, Pisa, Italy; 7: Novartis Vaccines, Siena, Italy
  • Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.AID-0023-2014
  • Received 22 August 2014 Accepted 04 September 2014 Published 21 November 2014
  • Ekaterina Dadachova, ekaterina.dadachova@einstein.yu.edu
image of Radiolabeled Antibodies for Therapy of Infectious Diseases
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Radiolabeled Antibodies for Therapy of Infectious Diseases, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/2/6/AID-0023-2014-1.gif /docserver/preview/fulltext/microbiolspec/2/6/AID-0023-2014-2.gif
  • Abstract:

    Novel approaches to the treatment of infectious diseases are urgently needed. This need has resulted in renewing the interest in antibodies for therapy of infectious diseases. Radioimmunotherapy (RIT) is a cancer treatment modality that utilizes radiolabeled monoclonal antibodies. During the last decade we have translated RIT into the field of experimental fungal, bacterial, and HIV infections. In addition, successful proof of principle experiments with radiolabeled pan-antibodies that bind to antigens shared by major pathogenic fungi have been performed . The armamentarium of pan-antibodies would result in reducing our dependence on microorganism-specific antibodies and thus would speed up the development of RIT for infections. We believe that the time is ripe for deploying RIT in the clinic to combat infectious diseases.

  • Citation: Dadachova E, Casadevall A. 2014. Radiolabeled Antibodies for Therapy of Infectious Diseases. Microbiol Spectrum 2(6):AID-0023-2014. doi:10.1128/microbiolspec.AID-0023-2014.

References

1. Dadachova E, Nakouzi A, Bryan R, Casadevall A. 2003. Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection. Proc Natl Acad Sci USA 100:10942–10947. [PubMed][CrossRef]
2. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23:525–530. [PubMed][CrossRef]
3. Larsen RA, Pappas PG, Perfect J, Aberg JA, Casadevall A, Cloud GA, James R, Filler S, Dismukes WE. 2005. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother 49:952–958. [PubMed][CrossRef]
4. Rhodes JC, Wicker LS, Urba WJ. 1980. Genetic control of susceptibility to Cryptococcus neoformans in mice. Infect Immun 29:494–499. [PubMed]
5. Jiang Z, Bryan RA, Morgenstern A, Bruchertseifer F, Casadevall A, Dadachova E. 2012. Treatment of early and established Cryptococcus neoformans infection with radiolabeled antibodies in immunocompetent mice. Antimicrob Agents Chemother 56:552–554. [PubMed][CrossRef]
6. Pai MP, Sakoglu U, Peterson SL, Lyons CR, Sood R. 2009. Characterization of BBB permeability in a preclinical model of cryptococcal meningoencephalitis using magnetic resonance imaging. J Cereb Blood Flow Metab 29:545–553. [PubMed][CrossRef]
7. Bryan RA, Jiang Z, Howell RC, Morgenstern A, Bruchertseifer F, Casadevall A, Dadachova E. 2010. Radioimmunotherapy is more effective than antifungal treatment in experimental cryptococcal infection. J Infect Dis 202:633–637. [PubMed][CrossRef]
8. Clemons KV, Stevens DA. 1998. Comparison of fungizone, Amphotec, AmBisome, and Abelcet for treatment of systemic murine cryptococcosis. Antimicrob Agents Chemother 42:899–902. [PubMed]
9. Kakeya H, Miyazaki Y, Senda H, Senda H, Kobayashi T, Seki M, Izumikawa K, Yamamoto Y, Yanagihara K, Tashiro T, Kohno S. 2008. Efficacy of SPK-843, a novel polyene antifungal, in a murine model of systemic cryptococcosis. Antimicrob Agents Chemother 52:1871–1872. [PubMed][CrossRef]
10. Bicanic T, Muzoora C, Brouwer AE, Brouwer AE, Meintjes G, Longley N, Taseera K, Rebe K, Loyse A, Jarvis J, Bekker LG, Wood R, Limmathurotsakul D, Chierakul W, Stepniewska K, White NJ, Jaffar S, Harrison TS. 2009. Independent association between rate of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clin Infect Dis 49:702–709. [PubMed][CrossRef]
11. Bryan RA, Jiang Z, Huang X, Morgenstern A, Bruchertseifer F, Sellers R, Casadevall A, Dadachova E. 2009. Radioimmunotherapy is effective against a high infection burden of Cryptococcus neoformans in mice and does not select for radiation-resistant phenotypes in cryptococcal cells. Antimicrob Agents Chemother 53:1679–1682. [PubMed][CrossRef]
12. Bryan RA, Huang X, Morgenstern A, Bruchertseifer F, Casadevall A, Dadachova E. 2008. Radio-fungicidal effects of external gamma radiation and antibody-targeted beta and alpha radiation on Cryptococcus neoformans. Antimicrob Agents Chemother 52:2232–2235. [PubMed][CrossRef]
13. Torosantucci A, Chiani P, Bromuro C, De Bernardis F, Palma AS, Liu Y, Mignogna G, Maras B, Colone M, Stringaro A, Zamboni S, Feizi T, Cassone A. 2009. Protection by anti-beta-glucan antibodies is associated with restricted beta-1,3 glucan binding specificity and inhibition of fungal growth and adherence. PLoS One 4:e5392. doi:10.1371/journal.pone.0005392. [PubMed][CrossRef]
14. Rachini A, Pietrella D, Lupo P, Torosantucci A, Chiani P, Bromuro C, Proietti C, Bistoni F, Cassone A, Vecchiarelli A. 2007. An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo. Infect Immun 75:5085–5094. [PubMed][CrossRef]
15. Torosantucci A, Bromuro C, Chiani P, De Bernardis F, Berti F, Galli C, Norelli F, Bellucci C, Polonelli L, Costantino P, Rappuoli R, Cassone A. 2005. A novel glyco-conjugate vaccine against fungal pathogens. J Exp Med 202:597–606. [PubMed][CrossRef]
16. Guimaraes AJ, Frases S, Gomez FJ, Zancope-Oliveira RM, Nosanchuk JD. 2009. Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum. Infect Immun 77:1357–1367. [PubMed][CrossRef]
17. Nosanchuk JD, Casadevall A. 2006. Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. Antimicrob Agents Chemother 50:3519–3528. [PubMed][CrossRef]
18. Bryan RA, Guimaraes AJ, Hopcraft S, Jiang Z, Bonilla K, Morgenstern A, Bruchertseifer F, Del Poeta M, Torosantucci A, Cassone A, Nosanchuk JD, Casadevall A, Dadachova E. 2012. Towards developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens. Mycopathologia 73:463–471. [PubMed][CrossRef]
19. Dadachova E, Burns T, Bryan RA, Apostolidis C, Brechbiel MW, Nosanchuk JD, Casadevall A, Pirofski L. 2004. Feasibility of radioimmunotherapy of experimental pneumococcal infection. Antimicrob Agents Chemother 48:1624–1629. [PubMed][CrossRef]
20. Rivera J, Nakouzi AS, Morgenstern A, Bruchertseifer F, Dadachova E, Casadevall A. 2009. Radiolabeled antibodies to Bacillus anthracis toxins are bactericidal and partially therapeutic in experimental murine anthrax. Antimicrob Agents Chemother 53:4860–4868. [PubMed][CrossRef]
21. Rivera J, Morgenstern A, Bruchertseifer F, Kearney JF, Turnbough CL, Jr, Dadachova E, Casadevall A. 2014. Microbicidal power of alpha radiation in sterilizing germinating Bacillus anthracis spores. Antimicrob Agents Chemother 58:1813–1815. [PubMed][CrossRef]
22. Dadachova E, Patel MC, Toussi S, Apostolidis C, Morgenstern A, Brechbiel MW, Gorny MK, Zolla-Pazner S, Casadevall A, Goldstein H. 2006. Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. PLoS Med 3:e427. doi:10.1371/journal.pmed.0030427. [PubMed][CrossRef]
23. Ho DD, Moudgil T, Alam M. 1989. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med 321:1621–1625. [PubMed][CrossRef]
24. Casadevall A, Goldstein H, Dadachova E. 2007. Targeting viruses-harboring host cells with radiolabeled antibodies. Expert Opin Biol Ther 7:595–597. [PubMed][CrossRef]
25. Dadachova E, Kitchen SG, Bristol G, Baldwin GC, Revskaya E, Empig C, Thornton GB, Gorny MK, Zolla-Pazner S, Casadevall A. 2012. Pre-clinical evaluation of a 213Bi-labeled 2556 antibody to HIV-1 gp41 glycoprotein in HIV-1 mouse models as a reagent for HIV eradication. PLoS One 7:e31866. doi:10.1371/journal.pone.0031866. [PubMed][CrossRef]
26. Mosier DE. 1996. Viral pathogenesis in hu-PBL-SCID mice. Sem Immunol 8:255–262. [PubMed][CrossRef]
27. Gigler A, Dorsch S, Hemauer A, Williams C, Kim S. 1999. Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins. J Virol 73:1974–1979. [PubMed]
28. Milenic DE, Brady ED, Brechbiel MW. 2004. Antibody-targeted radiation cancer therapy. Nat Rev Drug Discov 3:488–499. [PubMed][CrossRef]
29. Uckun FM, Rajamohan F, Pendergrass S, Ozer Z, Waurzyniak B, Mao C. 2003. Structure-based design and engineering of a nontoxic recombinant pokeweed antiviral protein with potent-anti-human immunodeficiency virus activity. Antimicrob Agents Chemother 47:1052–1061. [PubMed][CrossRef]
30. Uckun FM, Qazi S, Pendergrass S, Lisowski E, Waurzyniak B, Chen CL, Venkatachalam TK. 2002. In vivo toxicity, pharmacokinetics, and anti-human immunodeficiency virus activity of stavudine-5′-(p-bromophenyl methoxyalaninyl phosphate) stampidine in mice. Antimicrob Agents Chemother 46:3428–3436. [CrossRef]
microbiolspec.AID-0023-2014.citations
cm/2/6
content/journal/microbiolspec/10.1128/microbiolspec.AID-0023-2014
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.AID-0023-2014
2014-11-21
2017-03-29

Abstract:

Novel approaches to the treatment of infectious diseases are urgently needed. This need has resulted in renewing the interest in antibodies for therapy of infectious diseases. Radioimmunotherapy (RIT) is a cancer treatment modality that utilizes radiolabeled monoclonal antibodies. During the last decade we have translated RIT into the field of experimental fungal, bacterial, and HIV infections. In addition, successful proof of principle experiments with radiolabeled pan-antibodies that bind to antigens shared by major pathogenic fungi have been performed . The armamentarium of pan-antibodies would result in reducing our dependence on microorganism-specific antibodies and thus would speed up the development of RIT for infections. We believe that the time is ripe for deploying RIT in the clinic to combat infectious diseases.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/microbiolspec/2/6/AID-0023-2014.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.AID-0023-2014&mimeType=html&fmt=ahah

Figures

Image of FIGURE 1

Click to view

FIGURE 1

Mechanisms of RIT efficacy against infections. (a) Direct targeting of microbial cells with the radiolabeled organism-specific antibodies. (b) Killing of virally infected host cells by targeting viral antigens expressed on the surface of infected cells. doi:10.1128/microbiolspec.AID-0023-2014.f1

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.AID-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Click to view

FIGURE 2

RIT of experimental fungal infections with Bi- and Re-labeled mAbs. (a) Kaplan-Meier survival curves for A/JCr mice infected i.v. with 10 cells 24 h prior to treatment with 50 to 200 μCi Re-labeled mAbs. Animals injected with phosphate-buffered saline or 50 μg cold 18B7 served as controls. (b) RIT of C57BL6 mice infected i.v. with 10 cells: CFUs in the brains and the lungs of RIT-treated and control mice. Mice were treated i.p. with either 100 μCi Bi-18B7 24 h postinfection, 100 μCi Re-18B7 24 h postinfection, or 100 μCi Re-18B7 48 h postinfection or were left untreated and sacrificed 75 days posttreatment. The detection limit of the method was 50 CFUs. No CFUs were found in the brains and lungs of mice treated with 100 μCi Bi-18B7, which are presented in the graph as 40 CFUs/organ. The asterisks show the groups in which the CFUs were significantly different from the untreated controls. (c) Comparison of RIT and amphotericin B efficacy toward melanized . CFUs in the lungs and brains of mice infected with melanized . AJ/Cr mice were infected i.v. with 3 × 10 cells and were given either 100 μCi Bi-18B7 RIT or amphotericin B at 1 μg/g body weight on days 1, 2, and 3 postinfection or combined treatment or left untreated. The detection limit of the method was 50 CFUs. No CFUs were found in the brains and lungs of mice infected with melanized cells and treated with RIT, which are presented in the graph as 40 CFUs/organ. (d) Median survival of AJ/Cr mice infected i.v. with 5 × 10 and treated 24 h later with 150 μCi Re-18B7 or 125 μCi Bi-18B7 mAb. CN, cells from ATCC; CN, cells recovered from mice treated with Re-18B7 mAb; CN, cells recovered from mice treated with Bi-18B7 mAb; Re RIT/CN, mice infected with CN and treated with Re-18B7; Bi RIT/CN, mice infected with CN and treated with Bi-18B7; Re RIT/CN, mice infected with CN and treated with Re-18B7; Bi RIT/CN, mice infected with CN and treated with Bi-18B7. (e, f) RIT with Bi-4E12 antibody to Hsp60: (e) RIT of ; (f) RIT of . Each experiment was performed three times, and the results shown are from one typical experiment. The CFUs for each antibody dose were plated in triplicate. doi:10.1128/microbiolspec.AID-0023-2014.f2

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.AID-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Click to view

FIGURE 3

RIT of bacterial infections. (a) , Bi-labeled mAbs in C57BL/6 mice. Mice were infected i.p. with 1,000 organisms 1 h before treatment with mAbs. (b) RIT of Sterne infection with Bi-labeled mAbs. Mice were infected 1 h prior to labeled-mAb treatment. Survival experiment was repeated three times with similar results. Controls include unlabeled mAbs given in the same amounts (15 μg) as radiolabeled mAbs. doi:10.1128/microbiolspec.AID-0023-2014.f3

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.AID-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Click to view

FIGURE 4

RIT of SCID mice injected intrasplenically with JR-CSF HIV-infected human PBMCs and treated with Re- and Bi-labeled human anti-gp41 mAbs 246-D (a) or 2556 (b). (a) Limiting coculture results for 246-D mAb. Mice received either 20 μg cold anti-gp41 mAb 246-D, 100 μCi (20 μg) Bi-1418 or 80 μCi (20 μg) Re-1418 as isotype-matching controls, 80 μCi (20 μg) Re-246-D, or 100 μCi (20 μg) Bi-246-D i.p. 1 h after injection of PBMCs. In some experiments mice were given 80 μCi (20 μg) Re-246-D i.p. 1 h prior to injection of HIV-infected PBMCs. (b) PCR data for RIT with 50, 100, and 200 μCi Bi-2556 mAb. The cold 2556, untreated mice, and matching activities of the irrelevant 1418 mAb were used as controls. doi:10.1128/microbiolspec.AID-0023-2014.f4

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.AID-0023-2014
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error