Chimeric antigen receptor-modified T Cells inhibit the growth and metastases of established tissue factor-positive tumors in NOG mice.
Chimeric antigen receptor-modified T Cells inhibit the growth and metastases of established tissue factor-positive tumors in NOG mice.
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DOI：
10.18632/oncotarget.14367
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发表时间：
2017-02-07
期刊：
影响因子：
--
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Zhang Q;Wang H;Li H;Xu J;Tian K;Yang J;Lu Z;Zheng J
嵌合抗原受体（CAR）修饰的T细胞（CAR T）是癌症患者的有希望的治疗选择。这种方法需要鉴定在实体瘤中表达的肿瘤特异性抗原靶标。我们开发了一种新的第三代CAR，针对组织因子（TF），一种在某些类型的肺癌，黑色素瘤和其他癌症中过表达的表面分子。首先，我们通过免疫组织化学方法证明了TF在非小细胞肺癌（NSCLC）的鳞状细胞癌和腺癌以及黑色素瘤中过表达。在TF阳性癌细胞的存在下，CAR修饰的T细胞（TF-CAR T）被高度活化，并在体外显示出对TF阳性癌细胞的特异性细胞毒性。在建立的s.c.在异种移植和肺转移模型中，TF-CAR T细胞可以显著抑制s.c. TF阳性癌细胞的异种移植和转移。此外，TF-CAR T细胞在体内的安全性评估显示，该治疗在小鼠中没有引起明显的毒性。总之，这些发现表明TF-CAR T细胞可能是治疗TF阳性癌症患者的新型潜在治疗剂。
Chimeric antigen receptor (CAR)-modified T cell (CAR T) is a promising therapeutic option for patients with cancer. Such an approach requires the identification of tumor-specific antigen targets that are expressed in solid tumors. We developed a new third-generation CAR directed against tissue factor (TF), a surface molecule overexpressed in some types of lung cancer, melanoma and other cancers. First, we demonstrated by immunohistochemistry that TF was overexpressed in squamous cell carcinoma and adenocarcinoma of non-small cell lung cancer (NSCLC) and melanoma using a human tissue microarray. In the presence of TF-positive cancer cells, the CAR-modified T cells (TF-CAR T) were highly activated and showed specific cytotoxicity to TF-positive cancer cells in vitro. In established s.c. xenograft and lung metastasis models, TF-CAR T cells could significantly suppress the growth of s.c. xenograft and metastasis of TF-positive cancer cells. Additionally, the safety evaluation of TF-CAR T cells in vivo showed that the treatment did not cause obvious toxicity in mice. Taken together, these findings indicate that TF-CAR T cells might be a novel potential therapeutic agent for the treatment of patients with TF-positive cancers.
影响因子：
2.9
作者：
Zhang Q;Liu X;Li C;Liao D;Ouyang Z;Zheng J;Song X
通讯作者：
Song X