Year: 2026
Type: article
Abstract: The unique ability of chimeric antigen receptor (CAR) T cells to infiltrate tissues is revolutionizing our perspectives for tackling severe, refractory and otherwise untreatable diseases. In HIV, CAR-T cells have been designed to target viral biomarkers, with limited success so far. Here, we investigated the possibility of redirecting CAR-T cells against a cellular biomarker of the HIV reservoir, the programmed cell death protein 1 (PD-1). We designed two second-generation 4-1BB-CARs using the scFv of either a blocking (bPD1-CAR) or a nonblocking (nbPD1-CAR) anti-PD-1 monoclonal antibody. The CAR avidity modulated T cell sensitivity, trogocytosis, and effector functions, independently of the PD-1 signaling domain. Both anti-PD-1 CAR-T cells could persist for 70 days in HIV-infected humanized mice, correlating with viral protection and a disruption of the lymphoid architecture in the white pulp of the spleen. Together, our results open strategic avenues for reducing the HIV reservoir by demonstrating the feasibility of depleting specific T cell subpopulations.
Source: Science Advances
Authors: Laura Ermellino, Riddhima Banga, Spiros Georgakis, Nicole P. Kadzioch, Francesco Procopio, Ana Alcaraz-Serna, Oscar Alfageme-Abello, Raphaël Porret, Rebecca Cecchin, Michail Orfanakis, Rachel Schelling, Cloé Brenna, Duy-Cat Can, Mathilde Foglierini, Oliver Y. Chén, Laurent Perez, Craig Fenwick, Matthieu Perreau, Constantinos Petrovas, Roberto F. Speck, Giuseppe Pantaleo, Yannick D. Muller
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4414303580