Selected Grantee Publications

Anti–PD-1 Chimeric Antigen Receptor T Cells Efficiently Target SIV-Infected CD4⁺ T Cells in Germinal Centers

Eichholtz et al., The Journal of Clinical Investigation. 2024.

https://pubmed.ncbi.nlm.nih.gov/38557496/

Researchers conducted adoptive transfer of anti–programmed cell death protein 1 (PD-1) chimeric antigen receptor (CAR) T cells in simian immunodeficiency virus (SIV)–infected rhesus macaques of both sexes on antiretroviral therapy (ART). In some macaques, anti–PD-1 CAR T cells expanded and persisted concomitant with the depletion of PD-1⁺ memory T cells—including lymph node CD4⁺ follicular helper T cells—associated with depletion of SIV RNA from the germinal center. Following CAR T infusion and ART interruption, SIV replication increased in extrafollicular portions of lymph nodes, plasma viremia was higher, and disease progression accelerated, indicating that anti–PD-1 CAR T cells depleted PD-1⁺ T cells and eradicated SIV from this immunological sanctuary. Supported by ORIP (U42OD011123, U42OD010426, P51OD010425, P51OD011092), NCI, NIAID, and NIDDK.