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Blood. 2013 Feb 28;121(9):1524-33. doi: 10.1182/blood-2012-07-447250. Epub 2012 Dec 20.

Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV.

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1
Department of Medicine and Center for AIDS Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Erratum in

  • Blood. 2014 Jul 24;124(4):663.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00295477.

Comment in

PMID:
23264589
PMCID:
PMC3587318
DOI:
10.1182/blood-2012-07-447250
[Indexed for MEDLINE]
Free PMC Article

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