Use of Viral Antigen as a Strategy to Drive HIV-1 Latency Reversal and Immune Targeting
Despite the success of antiretroviral therapy (ART), latent HIV-1 continues to persist in a long-lived population of resting memory CD4+ T cells. Cells from the latent HIV reservoir can re-activate at any time. Finding a safe and effective means to induce latency reversal (LR) during ART to expose the HIV-1 cellular reservoir for immune elimination has been a major barrier to achieving a functional cure.
Description
Pitt researchers have used antigen-presenting type 1-polarized monocyte-derived dendritic cells (MDC1) generated from chronic HIV-1-infected individuals on ART as a means to induce HIV-1 latency reversal in autologous CD4+ T cells harboring replication-competent provirus. These antigen-presenting MDC1 activated the expansion of cytotoxic T cells (CTL) capable of killing the exposed HIV-1-infected targets and could serve as both a targeted means to safely unmask antigen-specific CD4+ T cells harboring HIV-1 and to support CTL responses that effectively target the MDC1-exposed HIV-1 cellular reservoir. This method of eliminating the latent HIV-1 cellular reservoir is a novel and exciting step towards a functional cure for HIV.Applications
· Treating HIV-1 infection· Identifying and isolating CD4+ T cells harboring HIV
Advantages
· Activates the expansion of cytotoxic T cells that kill HIV-1-infected targets· Makes CD4+ T cells harboring latent HIV-1 vulnerable to antiretroviral therapy and immune elimination
Invention Readiness
In vitro dataIP Status
https://patents.google.com/patent/US20220249653A1Related Publication(s)
Kristoff, J., Palma, M. L., Garcia-Bates, T. M., Shen, C., Sluis-Cremer, N., Gupta, P., Rinaldo, C. R., & Mailliard, R. B. (2019). Type 1-programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1. EBioMedicine, 43, 295–306. https://doi.org/10.1016/j.ebiom.2019.03.077