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• W3033147075 abstract "Chimeric antigen receptor T cells (CAR-T cells) therapy has been well recognized for treating B cell-derived malignancy. However, the efficacy of CAR-T cells against solid tumors remains dissatisfactory, partially due to the heterogeneity of solid tumors and T cell exhaustion in tumor microenvironment. PD-L1 is up-regulated in multiple solid tumors, resulting in T cell exhaustion upon binding to its receptor PD-1.Here, we designed a dominant-negative form of PD-1, dPD1z, a vector containing the extracellular and transmembrane regions of human PD-1, and a CAR vector against PD-L1, CARPD-L1z, a vector employs a high-affinity single-chain variable fragment (scFv) against human PD-L1. These two vectors shared the same intracellular structure, including 4-1BB and TLR2 co-stimulatory domains, and the CD3ζ signaling domain.dPD1z T and CARPD-L1z T cells efficiently lysed PD-L1+ tumor cells and had enhanced cytokine secretion in vitro and suppressed the growth of non-small cell lung cancer (NSCLC), gastric cancer and hepatoma carcinoma in patient-derived xenograft (PDX). However, the combination of anti-mesothelin CAR-T cells (CARMSLNz T) with dPD1z T or CARPD-L1z T cells did not repress tumor growth synergistically in PDX, as CARMSLNz T cells upregulated PD-L1 expression upon activation and were subsequently attacked by dPD1z T or CARPD-L1z T cells.In conclusion, we demonstrate CAR-T cells targeting PD-L1 were effective for suppressing the growth of multiple types of solid tumors in PDX models though their safety needs to be carefully examined." @default.
• W3033147075 created "2020-06-12" @default.
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• W3033147075 date "2020-06-03" @default.
• W3033147075 modified "2023-10-15" @default.
• W3033147075 title "Chimeric antigen receptor T cells targeting PD-L1 suppress tumor growth" @default.
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• W3033147075 doi "https://doi.org/10.1186/s40364-020-00198-0" @default.
• W3033147075 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7268496" @default.
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• W3033147075 hasPublicationYear "2020" @default.
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