AI Article Synopsis

  • Researchers used retroviral vectors to genetically modify T cells with CD4-chimeric antigen receptors (CARs) to enhance their ability to target and kill HIV-infected cells.
  • The study involved stimulating rhesus monkey T cells and measuring their effectiveness in killing HIV-infected cells using impedance as a measure of success.
  • The results indicated that a significant portion of the modified T cells could effectively target and kill HIV-infected cells, suggesting a potential new approach to HIV treatment that could eliminate the need for traditional therapies like HAART.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318253PMC
http://dx.doi.org/10.1111/jmp.12137DOI Listing

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