Enhance anti-lung tumor efficacy of chimeric antigen receptor-T cells by ectopic expression of C-C motif chemokine receptor 6

• 作者: Liyuan Jin Lei Cao Yingjie Zhu Jiani Cao Xiaoyan Li Jianxia Zhou Bing Liu Tongbiao Zhao
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2021,（8）
• 所属期刊栏目: ARTICLES
• 页码范围: 803-812
• 页数: 10页
• 语种: 英文

摘要

Chimeric antigen receptor-T (CAR-T) cells have limited therapeutic efficacy against solid tumors,partially due to their limited ability to reach and invade into the neoplastic foci.By gene expression profiling interactive analysis,we identified that the C-C motif chemokine ligand (CCL) 20 is highly expressed in lung and other most incidence and/or mortality cancers such as colon,rectum,stomach,and liver cancers.Forced expression of C-C motif chemokine receptor 6 (CCR6),the biunique receptor of CCL20,results in robust trafficking of CAR-T cells toward CCL20-secreting tumor cells.In a lung cancer xenograft mouse model,CCR6-expressing CAR-T cells efficiently migrate to and infiltrate into solid tumors upon infusion,leading to effective tumor clearance and significantly prolonged survival of tumor-bearing mice.In addition,culturing CCR6-CAR-T cells with interleukin (IL)-7 and IL-15 further improved their anti-lung cancer activity.Our findings provide supporting evidence for the clinical development of chemokine receptorengineered CAR-T cells for solid tumor immunotherapy.