Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins

Ekaterina Dadachova, Mahesh C. Patel, Sima Toussi, Christos Apostolidis, Alfred Morgenstern, Martin W. Brechbiel, Miroslaw K. Gorny, Susan Zolla-Pazner, Arturo Casadevall, Harris Goldstein

Research output: Contribution to journalArticle

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Abstract

Background: The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. Methods and Findings: Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 (213Bi) and rhenium 188 (188Re) selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs) in vitro. Treatment of severe combined immunodeficiency (SCID) mice harboring HIV-1-infected hPBMCs in their spleens with a 213Bi- or 188Re-labeled monoclonal antibody (mAb) to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the 188Re-labeled antibody to gp41 compared with those treated with the 188Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. Conclusions: The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV.

Original languageEnglish (US)
Pages (from-to)2094-2103
Number of pages10
JournalPLoS Medicine
Volume3
Issue number11
DOIs
StatePublished - Nov 2006

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Viral Proteins
HIV-1
Antibodies
Severe Combined Immunodeficiency
Monoclonal Antibodies
HIV
Blood Cells
Spleen
HIV Envelope Protein gp120
Rhenium
Radioimmunotherapy
Therapeutics
Western World
Bismuth
Highly Active Antiretroviral Therapy
Thymocytes
Radioisotopes
T-Lymphocytes
Transplants
Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dadachova, E., Patel, M. C., Toussi, S., Apostolidis, C., Morgenstern, A., Brechbiel, M. W., ... Goldstein, H. (2006). Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. PLoS Medicine, 3(11), 2094-2103. https://doi.org/10.1371/journal.pmed.0030427

Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. / Dadachova, Ekaterina; Patel, Mahesh C.; Toussi, Sima; Apostolidis, Christos; Morgenstern, Alfred; Brechbiel, Martin W.; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Casadevall, Arturo; Goldstein, Harris.

In: PLoS Medicine, Vol. 3, No. 11, 11.2006, p. 2094-2103.

Research output: Contribution to journalArticle

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 Medicine, vol. 3, no. 11, pp. 2094-2103. https://doi.org/10.1371/journal.pmed.0030427
Dadachova E, Patel MC, Toussi S, Apostolidis C, Morgenstern A, Brechbiel MW et al. Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. PLoS Medicine. 2006 Nov;3(11):2094-2103. https://doi.org/10.1371/journal.pmed.0030427
Dadachova, Ekaterina ; Patel, Mahesh C. ; Toussi, Sima ; Apostolidis, Christos ; Morgenstern, Alfred ; Brechbiel, Martin W. ; Gorny, Miroslaw K. ; Zolla-Pazner, Susan ; Casadevall, Arturo ; Goldstein, Harris. / Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. In: PLoS Medicine. 2006 ; Vol. 3, No. 11. pp. 2094-2103.
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