Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety.
Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety.
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DOI：
10.1038/s41565-021-00982-5
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发表时间：
2021-12
影响因子：
38.3
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Nguyen NT;Huang K;Zeng H;Jing J;Wang R;Fang S;Chen J;Liu X;Huang Z;You MJ;Rao A;Huang Y;Han G;Zhou Y
FDA 批准的嵌合抗原受体 (CAR) T 细胞免疫疗法在血液恶性肿瘤患者中显示出治疗潜力。然而，由于缺乏对抗肿瘤免疫反应的部位和持续时间的控制，CAR T细胞疗法仍然面临着细胞因子释放综合征和靶向脱瘤毒性带来的重大安全挑战。在此，我们提出了光可切换 CAR T 细胞（称为“LiCAR-T”）的设计，它允许实时光可调激活治疗性 T 细胞，从而精确诱导肿瘤细胞杀伤。当与成像引导、手术可移除的上转换纳米板 (UCNP) 结合使用时，LiCAR T 细胞能够在体内对 T 细胞介导的抗肿瘤治疗活性进行空间和时间控制，并大大减轻副作用。我们的纳米光遗传学免疫调节平台不仅提供了一种独特的方法来研究 CAR 介导的抗肿瘤免疫，而且还为开发精准医学以提供个性化抗癌治疗奠定了基础。
FDA-approved chimeric antigen receptor (CAR) T cell-based immunotherapy has shown curative potential in patients with hematological malignancies. However, owing to the lack of control over the location and duration of anti-tumor immune response, CAR T-cell therapy still faces significant safety challenges arising from cytokine release syndrome and on-target off-tumor toxicity. Herein, we present the design of light-switchable CAR T-cells (designated “LiCAR-T”) that allow real-time photo-tunable activation of therapeutic T cells to precisely induce tumor cell killing. When coupled with imaging-guided, surgically removable upconversion nanoplates (UCNPs) that have enhanced near infrared (NIR)-to-blue upconversion luminescence as miniature deep tissue photon-transducers, LiCAR T-cells enable both spatial and temporal control over T cell-mediated anti-tumor therapeutic activity in vivo with greatly mitigated side effects. Our nano-optogenetic immunomodulation platform not only provides a unique approach to interrogate CAR-mediated anti-tumor immunity, but also sets the stage for developing precision medicine to deliver personalized anti-cancer therapy.
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影响因子：
82.9
作者：
Giavridis T;van der Stegen SJC;Eyquem J;Hamieh M;Piersigilli A;Sadelain M
通讯作者：
Sadelain M
影响因子：
48
作者：
Kennedy, Matthew J.;Hughes, Robert M.;Peteya, Leslie A.;Schwartz, Joel W.;Ehlers, Michael D.;Tucker, Chandra L.
通讯作者：
Tucker, Chandra L.
DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
影响因子：
4
作者：
Nguyen NT;Ma G;Lin E;D'Souza B;Jing J;He L;Huang Y;Zhou Y
通讯作者：
Zhou Y
影响因子：
28.2
作者：
Sadelain M;Brentjens R;Rivière I
通讯作者：
Rivière I