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Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV.
- Source :
-
Blood . 2/28/2013, Vol. 121 Issue 9, p1524-1533. 10p. - Publication Year :
- 2013
-
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]
- Subjects :
- *T cells
*VIREMIA
*BLOODBORNE infections
*SEPSIS
*VIRUS diseases
Subjects
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 121
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 85909121
- Full Text :
- https://doi.org/10.1182/blood-2012-07-447250