HIV specific t cells expressing an X5–GPI artificial receptor can suppress hiv replication in vitro—implications for a cure strategy for HIV+ individuals with hematologic malignancies

      Polyclonal, polyfunctional multi-antigen HIV-specific T cells (HXTC) derived from both HIV positive and HIV negative individuals, suppress active HIV replication in vitro—providing a promising platform for mediating a functional HIV cure in the context of allogeneic stem cell transplant (SCT). While the inclusion of cytotoxic CD4+ T cells in T cell products has been shown to enhance in vivo persistence, in the HIV setting, the risks for infection is a limitation. To address this, we propose providing resistance to HXTC by using a broadly neutralizing HIV antibody directed against the X5 portion of HIV envelope. We hypothesized that expression of this protein via a GPI artificial receptor on HXTC would prevent infection as the GPI (glycosyl-phosphatidylinositol) signal targets the X5 scFv for expression on lipid rafts, placing it in close proximity to CD4. Hence, during HIV infection of a CD4 T cell, the X5-GPI AR can potentially recognize the transiently exposed X5 epitope on gp120 and block the fusion step.
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