Maclean A.G.,Tulane National Primate Research Center Covington |
Walker E.,Tulane National Primate Research Center Covington |
Sahu G.K.,Roger William Medical Center Providence |
Skowron G.,Roger William Medical Center Providence |
And 4 more authors.
Journal of Medical Primatology | Year: 2014
Background: To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD4-chimeric antigen receptors (CARs) to genetically modify autologous T cells and redirect CTL toward HIV. The CD4 extracellular domain targets envelope and the intracellular signaling domains activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral replication. Methods: We stimulated rhesus PBMCs with antibodies to CD3/CD28 and cotransduced T cells with CD4-CAR and maC46 vectors. CD4-CAR-transduced T cells were added to Env+ 293T cells at E:T of 1:1. Killing of target cells was measured as reduced impedance. Results: We observed gene expression in 60-70% of rhesus CD3+CD8+ T cells with the individual vectors and in 35% of the cells with both vectors. CD4-CAR-transduced populations specifically killed Env+ cells. Conclusions: In these studies, we showed that designer T cells were redirected to kill Env+ cells. Control of viremia without HAART would revolutionize treatment for HIV patients. © 2014 John Wiley & Sons A/S. Source