1. Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV.
- Author
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Tebas, Pablo, Stein, David, Binder-Scholl, Gwendolyn, Mukherjee, Rithun, Brady, Troy, Rebello, Tessio, Humeau, Laurent, Kalos, Michael, Papasawas, Emmanouil, Montaner, Luis J., Schullery, Daniel, Shaheen, Farida, Brennan, Andrea L., Zhaohui Zheng, Cotte, Julio, Slepushkin, Vladimir, Veloso, Elizabeth, Mackley, Adonna, Wei-Ting Hwang, and Aberra, Faten
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T cells , *VIREMIA , *BLOODBORNE infections , *SEPSIS , *VIRUS diseases - Abstract
We report the safety and tolerability of 87 infusions of lentiviral vector-modified autologous CD4 T cells (VRX496-T; trade name, Lexgenleucel-T) in 17 HIV patients with well-controlled viremia. Antiviral effects were studied during analytic treatment interruption in a subset of 13 patients. VRX496-T was associated with a decrease in viral load set points in 6 of 8 subjects (P = .08). In addition, A→ G transitions were enriched in HIV sequences after infusion, which is consistent with a model in which transduced CD4 T cells exert antisense-mediated genetic pressure on HIV during infection. Engraftment of vector-modified CD4 T cells was measured in gut-associated lymphoid tissue and was correlated with engraftment in blood. The engraftment half-life in the blood was approximately 5 weeks, with stable persistence in some patients for up to 5 years. Conditional replication of VRX496 was detected periodically through 1 year after infusion. No evidence of clonal selection of lentiviral vector-transduced T cells or integration enrichment near oncogenes was detected. This is the first demonstration that gene-modified cells can exert genetic pressure on HIV. We conclude that gene-modified T cells have the potential to decrease the fitness of HIV-1 and conditionally replicative lentiviral vectors have a promising safety profile in T cells. This study is registered at www.clinicaltrials.gov as number NCT00295477. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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