Lenalidomide Enhances CAR-T Cell Activity Against Solid Tumor Cells

Author:

Wang Zhixiong123,Zhou Guomin1,Risu Na3,Fu Jiayu3,Zou Yan4,Tang Jiaxing4,Li Long4,Liu Hui1,Liu Qian1,Zhu Xuekai4ORCID

Affiliation:

1. School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, China

2. Ma’anshan University, China

3. Division of Health Science, Graduate School of Medicine, Osaka University, Japan

4. Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, China

Abstract

Chimeric antigen receptor (CAR) T-cell immunotherapy still faces many challenges in the treatment of solid tumors, one of which is T-cell dysfunction or exhaustion. Immunomodulator lenalidomide may improve CAR T-cell function. In this study, the effects of lenalidomide on CAR T-cell functions (cytotoxicity, cytokine secretion, and cell proliferation) were investigated. Two different CAR T cells (CD133-specific CAR and HER2-specific CAR) were prepared, and the corresponding target cells including human glioma cell line U251 CD133-OE that overexpress CD133 and human breast cancer cell line MDA-MB-453 were used for functional assay. We found that lenalidomide promoted the killing of U251 CD133-OE by CD133-CAR T cells, the cytokine secretion, and the proliferation of CD133-CAR T cells. Lenalidomide also enhanced the cytotoxicity against MDA-MB-453 and the cytokine secretion of HER2-CAR T cells but did not affect their proliferation significantly. Furthermore, lenalidomide may regulate the function of CAR T cells by inducing the degradation of transcription factors Ikaros and Aiolos.

Funder

National Key R&D Program of China

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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