Multicolor Light-Induced Immune Activation via Polymer Photocaged Cytokines.
Multicolor Light-Induced Immune Activation via Polymer Photocaged Cytokines.
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DOI：
10.1021/acs.biomac.2c01207
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发表时间：
2023-03-13
影响因子：
6.2
通讯作者：
Dreaden, Erik C.
中科院分区：
文献类型：
--
作者：
Birnbaum, Lacey A.;Sullivan, Emily C.;Do, Priscilla;Uricoli, Biaggio;Raikar, Sunil S.;Porter, Christopher C.;Henry, Curtis J.;Dreaden, Erik C.
细胞因子作为人类免疫系统的有效细胞外信号，可以在患有自身免疫性疾病、组织损伤和癌症的患者中引起显着的治疗反应。然而，尽管它们具有治疗潜力，重组细胞因子介导的免疫反应仍然难以控制，因为它们的施用通常是全身性的，而它们的预期作用位点是局部的。为了解决空间和时间上限制细胞因子信号的挑战，我们最近设计了一种策略，通过对可见 LED 光做出反应的光不稳定聚合物进行化学修饰，使重组细胞因子可逆失活。扩展这种方法以实现体内和多色免疫激活，在这里我们描述了一种策略，利用组织穿透的近红外（NIR）光选择性地重新激活附加有七次甲基花青-聚乙二醇的细胞因子。我们发现，笼状促炎细胞因子的近红外 LED 光照明可恢复同源受体信号传导，并增强 T 细胞参与癌症离体免疫疗法的活性。使用可见光和近红外响应细胞因子的组合，我们进一步证明了离体 T 细胞细胞溶解的多波长光学控制，以及使用彩色光和正交光笼细胞因子对作为输入和 T 细胞活性作为输出执行布尔逻辑的能力。总之，这项工作展示了一种利用光控制细胞外免疫细胞信号的新方法，这种策略在未来可能会提高我们对癌症和其他疾病的理解和治疗能力。
Cytokines act as potent, extracellular signals of the human immune system and can elicit striking treatment responses in patients with autoimmune disease, tissue damage, and cancer. Yet, despite their therapeutic potential, recombinant cytokine-mediated immune responses remain difficult to control as their administration is often systemic, whereas their intended sites of action are localized. To address the challenge of spatially and temporally constraining cytokine signals, we recently devised a strategy whereby recombinant cytokines are reversibly inactivated via chemical modification with photo-labile polymers that respond to visible LED light. Extending this approach to enable both in vivo and multicolor immune activation, here we describe a strategy whereby cytokines appended with heptamethine cyanine-polyethylene glycol are selectively re-activated ex vivo using tissue-penetrating near-infrared (NIR) light. We show that NIR LED light illumination of caged, pro-inflammatory cytokines restores cognate receptor signaling and potentiates the activity of T cell-engager cancer immunotherapies ex vivo. Using combinations of visible- and NIR-responsive cytokines, we further demonstrate multiwavelength optical control of T cell cytolysis ex vivo, as well as the ability to perform Boolean logic using multicolored light and orthogonally photocaged cytokine pairs as inputs and T cell activity as outputs. Together, this work demonstrates a novel approach to control extracellular immune cell signals using light, a strategy that in the future may improve our understanding of and ability to treat cancer and other diseases.
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影响因子：
17.1
作者：
Eskandari SK;Sulkaj I;Melo MB;Li N;Allos H;Alhaddad JB;Kollar B;Borges TJ;Eskandari AS;Zinter MA;Cai S;Assaker JP;Choi JY;Al Dulaijan BS;Mansouri A;Haik Y;Tannous BA;van Son WJ;Leuvenink HGD;Pomahac B;Riella LV;Tang L;Seelen MAJ;Irvine DJ;Azzi JR
通讯作者：
Azzi JR
捕获单小鼠生发中心之间克隆组成的变化。
影响因子：
7.7
作者：
Firl DJ;Degn SE;Padera T;Carroll MC
通讯作者：
Carroll MC
影响因子：
14.8
作者：
Meijer EFJ;Jeong HS;Pereira ER;Ruggieri TA;Blatter C;Vakoc BJ;Padera TP
通讯作者：
Padera TP
DOI：
10.1038/s41568-022-00491-0
发表时间：
2022-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Laskowski TJ;Biederstädt A;Rezvani K
通讯作者：
Rezvani K
影响因子：
28.1
作者：
Mansurov, Aslan;Hosseinchi, Peyman;Hubbell, Jeffrey A.
通讯作者：
Hubbell, Jeffrey A.