Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals |
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Authors: | Morgan Richard A Walker Robert Carter Charles S Natarajan Ven Tavel Jorge A Bechtel Chris Herpin Betsy Muul Linda Zheng Zhili Jagannatha Shyla Bunnell Bruce A Fellowes Vicki Metcalf Julia A Stevens Randy Baseler Michael Leitman Susan F Read Elizabeth J Blaese R Michael Lane H Clifford |
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Affiliation: | National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
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Abstract: | The present study examined the safety and relative in vivo survival of genetically engineered CD4+ T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. Ten pairs of identical twins discordant for HIV infection were recruited, with the uninfected twin serving as the lymphocyte donor. Ten subjects were treated with a total of 19 separate infusions of retroviral vector-transduced CD4+ enriched T cells. Control (neo gene) or anti-HIV gene (antisense trans-activation response [TAR] element and/or trans-dominant Rev)-engineered lymphocytes were monitored in peripheral blood for 3 years, using a vector-specific PCR assay. Data from 9 of the 10 patients (15 of the 19 infusions) demonstrated preferential survival of CD4+ lymphocytes containing the anti-HIV gene(s) in the immediate weeks after infusion. In six of six patients studied long term (>100 weeks), only T cells containing the anti-HIV genes were consistently detected. In addition, a marked survival advantage of anti-HIV gene-containing T cells was observed in a patient treated during a period of high viral load. Thus, these data strongly support the hypothesis that anti-HIV genes afford a survival advantage to T cells and potential benefit to HIV-1+ individuals. |
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