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Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy
Immune Network ( IF 6 ) Pub Date : 2016-01-01 , DOI: 10.4110/in.2016.16.2.134
Jae Hun Shin 1 , Hyung Bae Park 2 , Kyungho Choi 3
Affiliation  

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

中文翻译:

增强表达 PD-1 诱饵的细胞毒性 T 淋巴细胞的抗肿瘤反应性

程序性死亡-1 (PD-1) 是肿瘤微环境中 T 淋巴细胞的强负调节因子。通过与肿瘤细胞上的 PD-1 配体 (PD-L1) 结合,T 细胞表面的 PD-1 抑制肿瘤浸润性 T 细胞的抗肿瘤反应性。使用阻断抗体系统阻断 PD-1 功能已在临床试验中显示出显着的治疗效果。然而,由于自身反应性淋巴细胞的激活,大约 10% 至 15% 的接受治疗的患者表现出严重的自身免疫反应。为了实现肿瘤特异性 T 细胞的选择性激活,我们通过逆转录病毒转导生成了表达 PD-1(PD-1 诱饵)显性失活缺失突变体的 T 细胞。PD-1 诱饵增加了抗原特异性 T 细胞的 IFN-γ 分泌,以响应表达同源抗原的肿瘤细胞。将表达 PD-1 诱饵的 T 细胞过继转移到荷瘤小鼠体内,增强了 T 细胞介导的肿瘤消退。因此,T 细胞特异性阻断 PD-1 可能是提高抗肿瘤 T 细胞治疗有效性和安全性的有用策略。
更新日期:2016-01-01
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