Magnetic Nanoclusters Armed with Responsive PD-1 Antibody Synergistically Improved Adoptive T-Cell Therapy for Solid Tumors.
Magnetic Nanoclusters Armed with Responsive PD-1 Antibody Synergistically Improved Adoptive T-Cell Therapy for Solid Tumors.
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DOI：
10.1021/acsnano.8b07141
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发表时间：
2019-02
期刊：
影响因子：
17.1
通讯作者：
Weidong Nie;Wei Wei-Wei;Liping Zuo;Chengliang Lv;Fan Zhang;Guihong Lu;Feng Li;Guanghao Wu; Li
中科院分区：
文献类型：
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作者：
Weidong Nie;Wei Wei-Wei;Liping Zuo;Chengliang Lv;Fan Zhang;Guihong Lu;Feng Li;Guanghao Wu; Li
Although adoptive T-cell therapy has been successful in hematological malignancy treatment, its application in solid tumors remains a great challenge. Here, using a pH-sensitive benzoic-imine bond and inverse electron-demand Diels-Alder cycloaddition, we prepared magnetic nanoclusters (NCs) armed with responsive PD-1 antibody (aP), which could then bind onto effector T cells due to their PD-1 expression. After adoptive transfer, the magnetization and superparamagnetism of NCs enabled us to magnetically recruit effector T cells and aP simultaneously to tumor sites with MRI guidance. Owing to the acidic intratumoral microenvironment, the benzoic-imine bond then hydrolyzed, leading to the release of aP. The therapeutic effects of adoptive T cells and free aP could thus be spatiotemporally coupled. As a result, we achieved inhibition of tumor growth with few side effects, demonstrating the great promise of such a chemical approach for safe and high-performance adoptive T-cell therapy against solid tumors.
