Safety and Efficacy of a tCD25 Preselective Combination Anti-HIV Lentiviral Vector in Human Hematopoietic Stem and Progenitor Cells. (17th February 2015)

• Record Type: Journal Article
• Authors: Barclay, Sharlie L.; Yang, Yimin; Zhang, Siruo; Fong, Ryan; Barraza, Alfonso; Nolta, Jan A.; Torbett, Bruce E.; Abedi, Mehrdad; Bauer, Gerhard; Anderson, Joseph S.
• Is Part Of: Stem cells. Volume 33:Number 3(2015:Mar.)
• Page Start: 870
• Page End: 879
• Publication Date: 2015-02-17
• Subjects: Hematopoietic cells -- Gene therapy -- Human immunodeficiency virus -- Lentiviral vector; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1919
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: The successful suppression of human immunodeficiency virus (HIV) in the "Berlin Patient" has highlighted the ability of HIV-resistant hematopoietic stem cells to offer a potential functional cure for HIV-infected patients. HIV stem cell gene therapy can mimic this result by genetically modifying a patient's own cells with anti-HIV genes. Previous attempts of HIV gene therapy have been hampered by a low percentage of transplanted HIV-resistant cells which has led to minimal clinical efficacy. In our current study, we have evaluated the in vitro and in vivo safety and efficacy of a truncated/mutated form of human CD25 preselective anti-HIV lentiviral vector in human hematopoietic stem cells. This preselective vector allows us to purify vector-transduced cells prior to transplantation so an increased percentage of gene-modified cells can be delivered. Here, we demonstrate the safety of this strategy with successful engraftment and multilineage hematopoiesis of transduced cells in a humanized NOD-RAG1−/−IL-2rγ−/− knockout mouse model. Efficacy was also demonstrated with significant protection from HIV-1 infection including maintenance of human CD4+ cell levels and a decrease in HIV-1 plasma viremia. Collectively, these results establish the utility of this HIV stem cell gene therapy strategy and bring it closer to providing a functional cure for HIV-infected patients. Stem Cells 2015;33:870–879