嵌合抗原受体
CCL19型
免疫系统
癌症研究
T细胞
白细胞介素21
免疫学
白细胞介素2受体
渗透(HVAC)
生物
趋化因子
趋化因子受体
材料科学
复合材料
作者
Keishi Adachi,Yosuke Kano,Tomohiko Nagai,Namiko Okuyama,Yukimi Sakoda,Koji Tamada
摘要
Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 × 19 CAR-T cell therapy. Depletion of recipient T cells before 7 × 19 CAR-T cell administration dampened the therapeutic effects of 7 × 19 CAR-T cell treatment, suggesting that CAR-T cells and recipient immune cells collaborated to exert anti-tumor activity. Following treatment of mice with 7 × 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.
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