药学学报, 2021, 56(9): 2485-2494
沈亦池, 范雪莲, 王飞, 陈刚. 基于树突状细胞的疫苗递送研究进展[J]. 药学学报, 2021, 56(9): 2485-2494.
SHEN Yi-chi, FAN Xue-lian, WANG Fei, CHEN Gang. Advances in dendritic cell-based vaccine delivery[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2485-2494.

沈亦池1, 范雪莲1, 王飞1, 陈刚1,2,3*
1. 扬州大学兽医学院 (比较医学研究院), 江苏 扬州 225009;
2. 扬州大学, 江苏高校动物重要疫病与人兽共患病防控协同创新中心, 江苏 扬州 225009;
3. 扬州大学, 教育部农业与农产品安全国际合作联合实验室, 江苏 扬州 225009
树突状细胞(dendritic cell,DC)是目前已知功能最强大的专职抗原递呈细胞(antigen presenting cell,APC),其在机体免疫反应的启动与调控中起着至关重要的作用。因此,基于DC的疫苗递送系统逐渐成为基础科研与临床治疗关注的热点。DC可以负载全细胞抗原、核酸、多肽、蛋白[新生抗原(neoantigen)]及纳米粒,进行抗原的加工递呈及体内靶向递送,以诱导机体产生特异性细胞免疫应答与体液免疫应答,用于肿瘤、微生物感染等多种疾病的预防与治疗。基于此技术制备的疫苗被称为DC疫苗,近年来DC疫苗研究取得了长足的进展,本文以DC特性、DC疫苗种类及其临床研究进展进行综述。
关键词:    树突状细胞      抗原      疫苗      适应性免疫      纳米粒     
Advances in dendritic cell-based vaccine delivery
SHEN Yi-chi1, FAN Xue-lian1, WANG Fei1, CHEN Gang1,2,3*
1. Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China;
2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China;
3. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
Dendritic cells (DCs) are the most powerful and professional antigen-presenting cells (APCs) known at present. They play vital roles in the initiation and regulation of immune responses in body. Therefore, DC-based vaccine delivery system has gradually become a hotspot of basic scientific research and clinical treatment. DCs can be loaded with whole-cell antigens, nucleic acids, peptides, proteins (such as neoantigens) and nanoparticles to induce specific cellular immune responses and humoral immune responses after antigen processing, presentation and targeting delivery in vivo for the prevention and treatment of various diseases including cancers and microorganism infections. Vaccine-based on this technique is called dendritic cell (DC) vaccines. Great process in DC vaccines has been achieved in recent years. Therefore, we reviewed the characteristics of DC, types of DC vaccines and their clinical research progress in this paper.
Key words:    dendritic cell    antigen    vaccine    adaptive immunity    nanoparticle   
收稿日期: 2021-03-28
DOI: 10.16438/j.0513-4870.2021-0452
基金项目: 国家自然科学基金资助项目(31900993);江苏高校优势学科建设工程资助项目(PAPD);江苏省高等学校大学生创新创业训练计划项目(创新类项目)(20191117102Y).
通讯作者: 陈刚,Tel/Fax:86-514-87931730,E-mail:gang_chen2015@163.com
Email: gang_chen2015@163.com
PDF(725KB) Free
沈亦池  在本刊中的所有文章
范雪莲  在本刊中的所有文章
王飞  在本刊中的所有文章
陈刚  在本刊中的所有文章

[1] Cabeza-Cabrerizo M, Cardoso A, Minutti CM, et al. Dendritic cells revisited[J]. Annu Rev Immunol, 2021, 39:131-166.
[2] Wang Y, Xiang Y, Xin VW, et al. Dendritic cell biology and its role in tumor immunotherapy[J]. J Hematol Oncol, 2020, 13:107.
[3] Harari A, Graciotti M, Bassani-Sternberg M, et al. Antitumour dendritic cell vaccination in a priming and boosting approach[J]. Nat Rev Drug Discov, 2020, 19:635-652.
[4] Gardner A, Pulido AM, Ruffell B. Dendritic cells and their role in immunotherapy[J]. Front Immunol, 2020, 11:924.
[5] Xie XF, Ding Q, Hou JG, et al. Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer[J]. Genet Mol Res, 2015, 14:7548-7555.
[6] Lapenta C, Donati S, Spadaro F, et al. Lenalidomide improves the therapeutic effect of an interferon-α-dendritic cell-based lymphoma vaccine[J]. Cancer Immunol Immun, 2019, 68:1791-1804.
[7] Koido S. Dendritic-tumor fusion cell-based cancer vaccines[J]. Int J Mol Sci, 2016, 17:828
[8] He J, Zheng R, Zhang ZH, et al. Collagen I enhances the efficiency and anti-tumor activity of dendritic-tumor fusion cells[J]. Oncoimmunology, 2017, 6:e1361094.
[9] Suo L, Wang F, Zhou GB, et al. Optimal concentration of calcium and electric field levels improve tetraploid embryo production by electrofusion in mice[J]. J Reprod Develop, 2009, 55:383-385.
[10] Sun TY, Yan W, Yang CM, et al. Clinical research on dendritic cell vaccines to prevent postoperative recurrence and metastasis of liver cancer[J]. Genet Mol Res, 2015, 14:16222-16232.
[11] Meng RR, Zhang YW, Zhao GS, et al. Recent progress in research of dendritic cell-based tumor vaccine[J]. Chin J Cancer Prev Treat (中华肿瘤防治杂志), 2012, 19:1597-1600.
[12] Wang B, Wang HM, Xu FY, et al. Relationship of dendritic cells and tumor immunity[J]. Chin J Cell Biol (中国细胞生物学学报), 2013, 35:1666-1671.
[13] Martin-Lluesma S, Graciotti M, Grimm AJ. Are dendritic cells the most appropriate therapeutic vaccine for patients with ovarian cancer?[J]. Curr Opin Biotech, 2020, 65:190-196.
[14] Landi A, Babiuk LA,van Drunen Littel-van den Hurk S. High transfection efficiency, gene expression, and viability of monocyte-derived human dendritic cells after nonviral gene transfer[J]. J Leukoc Biol, 2007, 82:849-860.
[15] Amano T, Kajiwara K, Yoshikawa K, et al. Antitumor effects of vaccination with dendritic cells transfected with modified receptor for hyaluronan-mediated motility mRNA in a mouse glioma model[J]. J Neurosurg, 2007, 106:638-645.
[16] Zhao X, Gu YZ, Song XR. Research progress of dendritic cells anti-tumor vaccine stimulated by mRNA[J]. Acta Pharm Sin (药学学报), 2019, 54:1818-1823.
[17] Tao R, Li L, Huang W, et al. Activation of human dendritic cells by recombinant modified vaccinia virus Ankara vectors encoding survivin and IL-2 genes in vitro[J]. Hum Gene Ther, 2010, 21:98-108.
[18] Rowe HM, Lopes L, Brown N, et al. Expression of vFLIP in a lentiviral vaccine vector activates NF-kappaB, matures dendritic cells, and increases CD8+T-cell responses[J]. J Virol, 2009, 83:1555-1562.
[19] Wang B, Han S, Lien L, et al. Lentiviral calnexin-modified dendritic cells promote expansion of high-avidity effector T cells with central memory phenotype[J]. Insect Sci, 2010, 128:43-57.
[20] Xin H. Active immunizations with peptide-DC vaccines and passive transfer with antibodies protect neutropenic mice against disseminated candidiasis[J]. Vaccine, 2016, 34:245-251.
[21] Yanagisawa R, Koizumi T, Koya T, et al. WT1-pulsed dendritic cell vaccine combined with chemotherapy for resected pancreatic cancer in a phase I study[J]. Anticancer Res, 2018, 38:2217-2225.
[22] Han Y, Wu Y, Yang C, et al. Dynamic and specific immune responses against multiple tumor antigens were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy[J]. J Transl Med, 2017, 15:64.
[23] Akbar SMF, Furukawa S, Yoshida O, et al. Induction of anti-HBs in HB vaccine nonresponders in vivo by hepatitis B surface antigen-pulsed blood dendritic cells[J]. J Transl Med, 2007, 47:60-66.
[24] Tregoning J, Brown E, Cheeseman H, et al. Vaccines for COVID-19[J]. Clin Exp Immunol, 2020, 202:162-192.
[25] Alexandrov L, Nik-Zainal S, Vvedge D, et al. Signatures of mutational processes in human cancer[J]. Nature, 2013, 500:415-421.
[26] Liu YT, Wu JJ, Yang QF, et al. Advances in neoantigens and tumor immunotherapy[J]. Tumor (肿瘤), 2019, 39:312-316.
[27] Carreno BM, Magrini V, Becker-Hapak M, et al. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells[J]. Science, 2015, 348:803-808.
[28] Zhang R, Yuan F, Shu Y, et al. Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models[J]. Cancer Immunol Immun, 2020, 69:135-145.
[29] Almeida JPM, Lin AY, Figueroa ER, et al. In vivo gold nanoparticle delivery of peptide vaccine induces anti-tumor immune response in prophylactic and therapeutic tumor models[J]. Small, 2015, 11:1453-1459.
[30] Lee IH, Kwon HK, An S, et al. Imageable antigen-presenting gold nanoparticle vaccines for effective cancer immunotherapy in vivo[J]. Angew Chem Int Ed Engl, 2012, 51:8800-8805.
[31] Niikura K, Matsunaga T, Suzuki T, et al. Gold nanoparticles as a vaccine platform:influence of size and shape on immunological responses in vitro and in vivo[J]. ACS Nano, 2013, 7:3926-3938.
[32] Tran TH, Tran TTP, Nguyen HT, et al. Nanoparticles for dendritic cell-based immunotherapy[J]. Int J Pharm, 2018, 542:253-265.
[33] Zhou Q, Zhang Y, Du J, et al. Different-sized gold nanoparticle activator/antigen increases dendritic cells accumulation in liver-draining lymph nodes and CD8+T cell responses[J]. ACS Nano, 2016, 10:2678-2692.
[34] Mou Y, Chen B, Zhang Y. Influence of iron oxide nanopraticles on presentation capacity of dendritic cells[J]. Int J Nanomed, 2011, 6:1779-1786.
[35] Jadidi-Niaragh F, Atyabi F, Rastegari A, et al. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice[J]. J Control Release, 2017, 246:46-59.
[36] Yang P, Song H, Qin Y, et al. Engineering dendritic-cell-based vaccines and PD-1 blockade in self-assembled peptide nanofibrous hydrogel to amplify antitumor T-cell immunity[J]. Nano Lett, 2018, 18:4377-4385.
[37] Yang W, Zhu G, Wang S, et al. In situ dendritic cell vaccine for effective cancer immunotherapy[J]. ACS Nano, 2019, 13:3083-3094.
[38] Grippin AJ, Wummer B, Wildes T, et al. Dendritic cell-activating magnetic nanoparticles enable early prediction of anti-tumor response with magnetic resonance imaging[J]. ACS Nano, 2019, 13:13884-13898.
[39] Xiang J, Xu L, Gong H, et al. Antigen-loaded upconversion nanoparticles for dendritic cell stimulation, tracking, and vaccination in dendritic cell-based immunotherapy[J]. ACS Nano, 2015, 9:6401-6411.
[40] Liu F, Sun J, Yu W, et al. Quantum dot-pulsed dendritic cell vaccines plus macrophage polarization for amplified cancer immunotherapy[J]. Biomaterials, 2020, 242:119928.
[41] Lu W, Arraes LC, Ferreira WT, et al. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection[J]. Nat Med, 2004, 10:1359.
[42] Bol KF, Schreibelt G, Gerritsen WR, et al. Dendritic cell-based immunotherapy:state of the art and beyond[J]. Clin Cancer Res, 2016, 22:1897-1906.
[43] Garg AD, Coulie PG, Van den Eynde BJ, et al. Integrating next-generation dendritic cell vaccines into the current cancer immunotherapy landscape[J]. Trends Immunol, 2017, 38:577-593.
[44] Melero I, Gaudernack G, Gerritsen W, et al. Therapeutic vaccines for cancer:an overview of clinical trials[J]. Nat Rev Clin Oncol, 2014, 11:509-524.
[45] Saxena M, Bhardwaj N. Re-emergence of dendritic cell vaccines for cancer treatment[J]. Trends Cancer, 2018, 4:119-137.
[46] Wculek SK, Cueto FJ, Mujal AM, et al. Dendritic cells in cancer immunology and immunotherapy[J]. Nat Rev Immunol, 2020, 20:7-24.
[47] Xi HB, Wang GX, Fu B, et al. Survivin and PSMA loaded dendritic cell vaccine for the treatment of prostate cancer[J]. Biol Pharm Bull, 2015, 38:827-835.
[48] Calmeiro J, Carrascal M, Tavares A, et al. Pharmacological combination of nivolumab with dendritic cell vaccines in cancer immunotherapy:an overview[J]. Pharmacol Res, 2021, 164:105309.
[49] Xing JL, Li HC, Ren WH. Experimental study of dendritic cell vaccine combined with anti-PD-LI antibody in the treatmnet of liver cancer in mice[J]. J Henan Univ (Med Sci)[河南大学学报(医学版)], 2019, 38:30-33.
[50] Sprooten J, Ceusters J, Coosemans A, et al. Trial watch:dendritic cell vaccination for cancer immunotherapy[J]. Oncoimmunology, 2019, 8:e1638212.
[51] Marchisone C, Pfeffer U, Del Grosso F, et al. Progress towards gene therapy for cancer[J]. J Exp Clin Canc Res, 2000, 19:261-270.
1.叶鑫宇, 梅林.基于黑磷量子点的光热效应在树突状细胞激活中的作用[J]. 药学学报, 2019,54(7): 1297-1302
2.赵星, 顾杨卓, 宋相容.mRNA致敏的树突状细胞用于肿瘤免疫治疗的研究进展[J]. 药学学报, 2019,54(10): 1818-1823
3.刘壹菲, 薛晓旭, 李正宜, 王军朋, 张祎捷.芹菜素对脾细胞中树突状细胞的成熟和功能的影响[J]. 药学学报, 2017,52(3): 397-402
4.李凤前;费轶博;苏华;胡晋红.疫苗口服接种及其微粒传输系统[J]. 药学学报, 2007,42(3): 245-251
5.冯利;周兴军;王世聪;姜杨;齐宪荣.单剂HBsAg-PLGA控释疫苗微球小鼠体内免疫学研究[J]. 药学学报, 2006,41(2): 132-137
6.狄维;王林;彭涛;王升启.基于肿瘤相关糖抗原的抗肿瘤疫苗研究进展[J]. 药学学报, 2005,40(7): 591-599
7.曹胜利;蔡孟深;石佑恩.含两种不同肽段的血吸虫多抗原肽疫苗的合成及其对BALB/c小鼠的免疫保护作用[J]. 药学学报, 2000,35(6): 421-425
8.曹胜利;秦致辉;蔡孟深;石佑恩.血吸虫多抗原肽疫苗的合成及生物活性[J]. 药学学报, 1999,34(5): 368-371
9.曹胜利;蔡孟深;石佑恩.含两种不同肽段的血吸虫多抗原肽疫苗的合成与生物活性[J]. 药学学报, 1999,34(10): 751-754
10.毛峰;王超;程铁明;蔡孟深;张春英;陶其敏.多肽研究——Ⅸ.乙型肝炎病毒表面抗原(HBsAg)Pre-S区域肽段的合成和抗原特异性测定[J]. 药学学报, 1992,27(6): 428-433