CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.
Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.
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综合来看,我们的数据提示,i.p.
构建第二代癌胚抗原(CEA)特异性CAR-T 细胞。在多种伴有腹腔内及腹腔外转移的PC动物模型中,分别经腹腔内或静脉(i.v.)给予CEA CAR-T 细胞。
在PC动物模型中,与全身静脉输注相比,腹腔内给药的CAR-T 细胞抗肿瘤活性更强。此外,腹腔内给药可产生持久效应并预防肿瘤复发,在伴腹腔内或腹腔外器官转移的PC模型中也表现出强效抗肿瘤活性。与全身给药相比,对于无腹膜癌但存在腹腔外肿瘤的动物,腹腔内转移CAR-T 细胞也带来更强的抗肿瘤活性。随后在胰腺癌动物模型中,腹腔内给予新构建的靶向前列腺干细胞抗原CAR-T 细胞,进一步证实了这一现象。
综上,研究数据提示,腹腔内给予CAR-T 细胞可能是有效治疗癌症的一种可靠递送途径。
We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells.
Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells.
Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.
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