Enhanced CAR-T activity against established tumors by polarizing human T cells to secrete interleukin-9

Lintao Liu, Enguang Bi, Xingzhe Ma, Wei Xiong, Jianfei Qian, Lingqun Ye, Pan Su, Qiang Wang, Liuling Xiao, Maojie Yang, Yong Lu, Qing Yi

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5902
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Nov 19 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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