Karsten Eichholz, Yoshinori Fukazawa, Christopher W Peterson, Francoise Haeseleer, Manuel Medina, Shelby Hoffmeister, Derick M Duell, Benjamin D Varco-Merth, Sandra Dross, Haesun Park, Caralyn S Labriola, Michael K Axthelm, Robert D Murnane, Jeremy V Smedley, Lei Jin, Jiaxin Gong, Blake J Rust, Deborah H Fuller, Hans-Peter Kiem, Louis J Picker, Afam A Okoye, Lawrence Corey
Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1+ memory T cells in blood and tissues, including lymph node CD4+ follicular helper T (TFH) cells...
April 1, 2024: Journal of Clinical Investigation