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 interacti...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.展开更多
基金supported by the National Key R&D Program of China(2018YFA0108402)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302)the National Natural Science Foundation of China(31720103907,31570995,and 31621004)。
文摘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.
