【摘 要】
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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
【机 构】
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State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration
论文部分内容阅读
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.
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