High-affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells

Russell W Cochrane(Medical University of South Carolina), Rob A. Robino(Medical University of South Carolina), Bryan Granger(Medical University of South Carolina), Eva Allen(Medical University of South Carolina), Silvia G. Vaena(Medical University of South Carolina), Martin J. Romeo(Medical University of South Carolina), Aguirre A. de Cubas(Medical University of South Carolina), Stefano Berto(Medical University of South Carolina), Leonardo M. R. Ferreira(Medical University of South Carolina)
Molecular Therapy — Methods & Clinical Development
November 18, 2024
10.1016/j.omtm.2024.101385
Cited by 23Open Access
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Abstract

CAR Tregs uniquely acquiring CD40L surface expression and producing IFN-γ. Interestingly, decreasing CAR antigen affinity reduced Teff cell gene expression and inflammatory cytokine production by CAR Tregs. Our findings showcase the impact of engineered receptor activation on Treg biology and support tailoring CAR constructs to Tregs for maximal therapeutic efficacy.

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