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Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9
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Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9
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Journal Article
Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9
2020
Overview
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, differentiate to IFN-γ and granzyme-B secreting effector memory T cells but remain as long-lived and hyperproliferative T cells. Our findings are important for the improvement of CAR-T cell-based immunotherapy for human cancers.
Antigen-specific IL9-secreting CD4 Th9 and CD8 Tc9 cells have been previously characterized for their anti-tumour properties. Here, the authors show that ex vivo polarized Th9/Tc9 human CAR-T cells display increased anti-tumor activity in pre-clinical haematological and solid cancer models compared to conventional IL-2 activated CAR-T cells.
Publisher
Nature Publishing Group UK,Nature Portfolio
Subject
/ 13/31
/ 38/109
/ 38/22
/ 38/39
/ 38/5
/ 38/88
/ 38/90
/ 38/91
/ Animals
/ Humanities and Social Sciences
/ Humans
/ Immunotherapy, Adoptive - methods
/ Interferon-gamma - metabolism
/ Mice
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
/ Receptors, Chimeric Antigen - metabolism
/ Science
