Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals

Richard A. Morgan, Robert Walker, Charles S. Carter, Ven Natarajan, Jorge A. Tavel, Chris Bechtel, Betsy Herpin, Linda Muul, Zhili Zheng, Shyla Jagannatha, Bruce A. Bunnell, Vicki Fellowes, Julia A. Metcalf, Randy Stevens, Michael Baseler, Susan F. Leitman, Elizabeth J. Read, R. Michael Blaese, H. Clifford Lane

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58 Scopus citations

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 irans-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.

Original languageEnglish
Pages (from-to)1065-1074
Number of pages10
JournalHuman Gene Therapy
Volume16
Issue number9
DOIs
StatePublished - Sep 2005

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    Morgan, R. A., Walker, R., Carter, C. S., Natarajan, V., Tavel, J. A., Bechtel, C., Herpin, B., Muul, L., Zheng, Z., Jagannatha, S., Bunnell, B. A., Fellowes, V., Metcalf, J. A., Stevens, R., Baseler, M., Leitman, S. F., Read, E. J., Blaese, R. M., & Lane, H. C. (2005). Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals. Human Gene Therapy, 16(9), 1065-1074. https://doi.org/10.1089/hum.2005.16.1065