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

Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Research Abstract Details 

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Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Abstract Text:

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

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 ((213)Bi) and rhenium 188 ((188)Re) 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 (213)Bi- or (188)Re-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 (188)Re-labeled antibody to gp41 compared with those treated with the (188)Re-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.

Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Publishing Authors By Initials

E Dadachova,MC Patel,S Toussi,C Apostolidis,A Morgenstern,MW Brechbiel,MK Gorny,S Zolla-Pazner,A Casadevall,H Goldstein,

For similar proteins: viral proteins research abstracts see: proteins: viral proteins research

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Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: PLoS medicine

VOLUME: 3

Page Numbers: e427

Journal Abbreviation: PLoS Med.

ISSN: 1549-1676

DAY: 3

MONTH: Nov

YEAR: 2006

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 101231360

Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Keywords Mesh Terms:

KEYWORDS: Viral Proteins

MESH TERMS: immunology

Chemical & Substance for Abstract: Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. Information

Substance Name: Bismuth

Registry Number: 7440-69-9

Grant and Affiliation Information for Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins.

AFFILIATION: Albert Einstein College of Medicine, Bronx, New York, United States of America. edadacho@aecom.yu.edu

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI48466

ACRONYM: AI

MEDLINETA: PLoS Med

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