| 论文编号: |
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| 第一作者所在部门: |
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| 中文论文题目: |
C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction |
| 英文论文题目: |
C3aR costimulation enhances the antitumor efficacy of CAR-T cell therapy through Th17 expansion and memory T cell induction |
| 作者: |
Lai, Peilong, Chen, Xiaomei, Wang, Yulian, Wang, Jinghua, Zhang, Yuchen, Geng, Suxia, Li, Peng, Du, Xin, Weng, Jianyu and Pei, Duanqing |
| 论文出处: |
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| 刊物名称: |
Journal of hematology & oncology |
| 年: |
2022 |
| 卷: |
15 |
| 期: |
1 |
| 页: |
68 |
| 联系作者: |
Duanqing Pei |
| 收录类别: |
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| 影响因子: |
23.168 |
| 摘要: |
Although chimeric antigen receptor (CAR)-modified adoptive T cell therapy is a promising immunotherapy for hematological malignancies, the efficacy improvement in relapsed/refractory acute lymphoblastic leukemia (ALL) with extramedullary infiltration and in multiple myeloma (MM) is still warranted. Since C3aR activation can promote the expansion of tumor-killing Th17 cells, we hypothesized that incorporating C3aR as a costimulatory domain would augment the antitumor activity of CAR-T. In this study, we introduced the C3aR domain into a CAR and generated BB-ζ-C3aR CAR-T targeting CD19 or BCMA. These new CAR-T exhibited a potent cytolytic ability to eradicate tumor cells expressing CD19 or BCMA in vitro. When administered intravenously to ALL or MM xenograft mouse models, BB-ζ-C3aR CAR-T reduced the tumor burden and improved the survival rate. Of note, these CAR-T could effectively eradicate subcutaneous CD19+ tumor cells, highlighting the therapeutic potential in extramedullary leukemia. Mechanistically, BB-ζ-C3aR CAR-T tended to exhibit a Th17 phenotype favoring tumor killing and suppressed Tregs. In addition, the induction of memory T cell in the BB-ζ-C3aR CAR-T cells indicated their long-term effects. Together, our findings suggest that the application of C3aR costimulation boosts the ability of CAR-T to eradicate aggressive tumor cells via Th17 expansion and memory T cell induction. |
| 英文摘要: |
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