Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer.
Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer.
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DOI：
10.1016/j.bioactmat.2021.03.031
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发表时间：
2021-11
影响因子：
18.9
通讯作者：
Gao X
中科院分区：
文献类型：
--
作者：
Nie W;Yu T;Liu X;Wang B;Li T;Wu Y;Zhou X;Ma L;Lin Y;Qian Z;Gao X
癌症的免疫抑制性肿瘤微环境（TME）强烈阻碍抗肿瘤免疫反应，从而导致免疫治疗的反应令人失望。趋化因子作用于白细胞的化学吸引和促进特性引起了人们对通过增加 TME 中免疫细胞的浸润来提高免疫治疗效率的兴趣。在这项研究中，开发了一种基于 DOTAP、MPEG-PCL-MPEG 和 FA-PEG-PCL-PEG-FA 自组装的叶酸 (FA) 修饰基因递送系统，即 F-PPPD，用于递送编码免疫刺激趋化因子 CKb11 的质粒。 F-PPPD纳米颗粒递送质粒CKb11（pCKb11），导致肿瘤细胞大量分泌CKb11，成功激活T细胞，抑制巨噬细胞的M2极化，促进树突状细胞（DC）成熟，促进自然杀伤（NK）细胞浸润，抑制免疫抑制细胞浸润 在肿瘤组织中。 F-PPPD/pCKb11 的施用也显着抑制了癌症进展。我们的研究证明了通过纳米技术实现的 pCKb11 递送，可以重塑免疫抑制性 TME，用于癌症治疗。免疫抑制性肿瘤微环境阻碍瘤内免疫反应。免疫基因疗法是一种新疗法，为癌症患者带来了曙光。非病毒载体在免疫基因治疗中显示出巨大的潜力。携带 CKb11 的 FA 修饰非病毒载体可激活抗癌免疫力。
The immunosuppressive tumor microenvironment (TME) of cancer strongly hinders the anti-tumor immune responses, thereby resulting in disappointing responses to immunotherapy. Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME. In this study, a folic acid (FA) -modified gene delivery system based on the self-assembly of DOTAP, MPEG-PCL-MPEG, and FA-PEG-PCL-PEG-FA, namely F-PPPD, was developed to deliver plasmids encoding the immunostimulating chemokine CKb11. The delivery of plasmid CKb11 (pCKb11) by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells, which successfully activated T cells, suppressed the M2 polarization of macrophages, promoted the maturation of dendritic cells (DCs), facilitated the infiltration of natural killer (NK) cells and inhibited the infiltration of immunosuppressive cells in tumor tissues. Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression. Our study demonstrated a nanotechnology-enabled delivery of pCKb11, that remodeled the immunosuppressive TME, for cancer treatment. Immunosuppressive tumor microenvironment hinders the intratumoral immune responses. Immunogene therapy is one of new therapies, which brings dawn to the cancer patients. Non-viral vectors have shown great potential in immunogene therapy. FA modified non-viral vector carrying CKb11 activates the immunity against cancer.
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影响因子：
2.3
作者：
Conlon, Kevin C.;Miljkovic, Milos D.;Waldmann, Thomas A.
通讯作者：
Waldmann, Thomas A.
影响因子：
12.4
作者：
Kishida, T;Asada, H;Mazda, O
通讯作者：
Mazda, O
影响因子：
8.8
作者：
Koebel, M.;Madore, J.;Ramus, S. J.;Clarke, B. A.;Pharoah, P. D. P.;Deen, S.;Bowtell, D. D.;Odunsi, K.;Menon, U.;Morrison, C.;Lele, S.;Bshara, W.;Sucheston, L.;Beckmann, M. W.;Hein, A.;Thiel, F. C.;Hartmann, A.;Wachter, D. L.;Anglesio, M. S.;Hogdall, E.;Jensen, A.;Hogdall, C.;Kalli, K. R.;Fridley, B. L.;Keeney, G. L.;Fogarty, Z. C.;Vierkant, R. A.;Liu, S.;Cho, S.;Nelson, G.;Ghatage, P.;Gentry-Maharaj, A.;Gayther, S. A.;Benjamin, E.;Widschwendter, M.;Intermaggio, M. P.;Rosen, B.;Bernardini, M. Q.;Mackay, H.;Oza, A.;Shaw, P.;Jimenez-Linan, M.;Driver, K. E.;Alsop, J.;Mack, M.;Koziak, J. M.;Steed, H.;Ewanowich, C.;DeFazio, A.;Chenevix-Trench, G.;Fereday, S.;Gao, B.;Johnatty, S. E.;George, J.;Galletta, L.;Goode, E. L.;Kjaer, S. K.;Huntsman, D. G.;Fasching, P. A.;Moysich, K. B.;Brenton, J. D.;Kelemen, L. E.
通讯作者：
Kelemen, L. E.
影响因子：
5.1
作者：
Bessis, N;GarciaCozar, FJ;Boissier, MC
通讯作者：
Boissier, MC
影响因子：
6.4
作者：
Hartmann, Lynn C.;Keeney, Gary L.;Low, Philip S.
通讯作者：
Low, Philip S.