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临床前研究中腹腔给药靶向癌胚抗原的 CAR-T 细胞是有效治疗结直肠癌腹膜癌病的稳健递送途径

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.

查看英文原题

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.

PubMed 2023/11/23(内容时间) Cytotherapy Q1 · IF 4.5(JCR 2025)

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研究概要

综合来看,我们的数据提示,i.p.

中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Qian S、Chen J、Zhao Y、Zhu X、Dai D、Qin L、Hong J、Xu Y
第一作者单位
Department of Surgery, Fundación Jiménez Díaz University Hospital, Madrid, Spain. Electronic address: siyuanqz@gmail.com.Spain
通讯作者单位
Chongqing Key Laboratory of Gene and Cell Therapy, Chongqing Precision Biotechnology Co Ltd, Chongqing, China. Electronic address: cqian8634@gmail.com.China
文献类型
非美国政府资助研究
期刊
Cytotherapy2024 Feb
原文标识
PubMed 37999667 · DOI 10.1016/j.jcyt.2023.10.007