biostudies-literatureLiu LNCI NIH HHSU.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer InstituteCancer Prevention and Research Institute of Texas5902https://www.ebi.ac.uk/biostudies/studies/S-EPMC7677397biostudies-literatureUnknown11(1)CAR-T cell therapy is effective for hematologic malignancies. However, considerable numbers of patients relapse after the treatment, partially due to poor expansion and limited persistence of CAR-T cells in vivo. Here, we demonstrate that human CAR-T cells polarized and expanded under a Th9-culture condition (T9 CAR-T) have an enhanced antitumor activity against established tumors. Compared to IL2-polarized (T1) cells, T9 CAR-T cells secrete IL9 but little IFN-γ, express central memory phenotype and lower levels of exhaustion markers, and display robust proliferative capacity. Consequently, T9 CAR-T cells mediate a greater antitumor activity than T1 CAR-T cells against established hematologic and solid tumors in vivo. After transfer, T9 CAR-T cells migrate effectively to tumors, differentiNature communicationsEnhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9.PMC7677397R01 CA211073R01 CA239255R01 CA200539R01 CA214811RR180044Ye LQian JBi ELiu LWang QXiao LSu PLu YYang MMa XYi QXiong WfalseEnhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9.CAR-T cell therapy is effective for hematologic malignancies. However, considerable numbers of patients relapse after the treatment, partially due to poor expansion and limited persistence of CAR-T cells in vivo. Here, we demonstrate that human CAR-T cells polarized and expanded under a Th9-culture condition (T9 CAR-T) have an enhanced antitumor activity against established tumors. Compared to IL2-polarized (T1) cells, T9 CAR-T cells secrete IL9 but little IFN-γ, express central memory phenotype and lower levels of exhaustion markers, and display robust proliferative capacity. Consequently, T9 CAR-T cells mediate a greater antitumor activity than T1 CAR-T cells against established hematologic and solid tumors in vivo. After transfer, T9 CAR-T cells migrate effectively to tumors, differenti2020-01-01T00:00:00Z2020 Nov2025-04-27T00:33:38.597Z2021-02-20T00:27:13ZS-EPMC76773973321455510.1038/s41467-020-19672-2