期刊
PLOS MEDICINE
卷 3, 期 11, 页码 2094-2103出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pmed.0030427
关键词
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资金
- Intramural NIH HHS Funding Source: Medline
- NHLBI NIH HHS [HL059842, R01 HL059725, R01 HL059842, HL 59725] Funding Source: Medline
- NIAID NIH HHS [R01 AI48466, R01 AI048466, R01 AI036085, AI60507, AI 36085, R56 AI060507, R37 AI033142, R01 AI033774, R01 AI060507, AI033142, AI033774, P30 AI051519, AI-051519, R01 AI033142, AI 27742, P30 AI027742] Funding Source: Medline
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 (Bi-213) and rhenium 188 (Re-188) 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 Bi-213- or Re-188-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 Re-188-labeled antibody to gp41 compared with those treated with the Re-188-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.
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