Aptamer-T Cell Targeted Therapy for Tumor Treatment Using Sugar Metabolism and Click Chemistry.,ACS Chemical Biology

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Aptamer-T Cell Targeted Therapy for Tumor Treatment Using Sugar Metabolism and Click Chemistry.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-05-13 , DOI: 10.1021/acschembio.0c00164
Chuan-Gang Liu ₁ , Yong Wang ₁ , Peng Liu ₁ , Qi-Li Yao ₁ , Yuan-Yuan Zhou ₁ , Chao-Fan Li ₁ , Qiu Zhao ₂ , Guang-Hui Liu ₃ , Xiao-Lian Zhang _{1,

3}

Affiliation

The development of a tumor-targeted immunotherapy is highly required. The most advanced application is the use of CD19 chimeric antigen receptor (CAR)T (CAR-T) cells to B cell malignancies, but there are still side effects including potential carcinogenicity of lentiviral or retroviral insertion into the host cell genome. Here, we developed a nonviral aptamer-T cell targeted strategy for tumor therapy. Tumor cells surface-specific ssDNA aptamers were conjugated to CD3⁺T cells (aptamer-T cells) using N-azidomannosamine (ManNAz) sugar metabolic cell labeling and click chemistry. We found that the aptamer-T cells could specifically target and bind to tumor cells (such as SGC-7901 gastric cancer cell and CT26 colon carcinoma cell) in vitro and in mice after adoptively transfer in. Aptamer-T cells led to significant regression in tumor volume due to being enriched at tumor microenvironment and producing strong cytotoxicity activities of CD3⁺T cells with enhanced perforin, granzyme B, CD107a, CD69, and FasL expression. Moreover, aptamer-T displayed even stronger antitumor effects than an anti-PD1 immune-checkpoint monoclonal antibody (mAb) treatment in mice and combination with anti-PD1 yielded synergic antitumor effects. This study uncovers the strong potential of the adoptive nonviral aptamer-T cell strategy as a feasible and efficacious approach for tumor-targeted immunotherapy application.

中文翻译：

使用糖代谢和Click化学疗法进行肿瘤治疗的适体T细胞靶向疗法。

高度需要开发靶向肿瘤的免疫疗法。最先进的应用是将CD19嵌合抗原受体（CAR）T（CAR-T）细胞用于B细胞恶性肿瘤，但仍然存在副作用，包括慢病毒或逆转录病毒插入宿主细胞基因组的潜在致癌性。在这里，我们开发了一种针对肿瘤治疗的非病毒适体-T细胞靶向策略。使用N-叠氮甘露糖胺（ManNAz）糖代谢细胞标记和点击化学，将肿瘤细胞表面特异性ssDNA适体缀合至CD3 ⁺ T细胞（适体T细胞）。我们发现适体-T细胞可以在体外特异性靶向并结合肿瘤细胞（例如SGC-7901胃癌细胞和CT26结肠癌细胞）Aptamer-T细胞由于在肿瘤微环境中富集并产生具有增强的穿孔素，颗粒酶B，CD107a，CD69和FasL表达的CD3 ⁺ T细胞而产生强大的细胞毒性，从而导致肿瘤体积显着退化。。此外，适体-T在小鼠中显示出比抗PD1免疫检查点单克隆抗体（mAb）更强的抗肿瘤作用，并且与抗PD1组合可产生协同抗肿瘤作用。这项研究揭示了过继的非病毒适体-T细胞策略作为肿瘤靶向免疫治疗应用的可行和有效方法的强大潜力。

更新日期：2020-06-19

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