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我从中国生物化学与分子生物学报上找到了一篇文章,感觉挺有意思的,在此分享给大家。

治疗性肿瘤疫苗:过去、现在和未来

摘要

肿瘤是机体在各种致瘤因素的作用下,局部细胞在基因水平上对其生长的调控失去控制,导致细胞异常增生而形成的新生物。根据肿瘤生物学特性及其对机体危害程度的不同,可将其分为良性和恶性肿瘤两大类。在中国,恶性肿瘤是导致患者死亡的主要原因之一,其发病率和死亡率不断攀升,成为非常严重的公共健康问题。肿瘤疫苗是一种利用肿瘤特异性抗原或肿瘤相关抗原激活机体特异性免疫应答,以杀伤肿瘤细胞的免疫干预策略,是肿瘤免疫治疗研究的热点之一。在过去的几十年里,随着基因技术的不断发展,肿瘤疫苗的研发取得了极大的进步。肿瘤疫苗在实体瘤的临床前研究及其相关试验中均显示出巨大的潜力,有望进一步提高患者的总生存期。根据作用目的,肿瘤疫苗可分为预防性肿瘤疫苗和治疗性肿瘤疫苗;根据作用机制,肿瘤疫苗又可分为细胞疫苗、蛋白质/合成肽疫苗、核酸疫苗等。目前,免疫检查点抑制剂、过继性细胞治疗和基于纳米材料的免疫疗法均在肿瘤治疗中显示出较好的疗效,肿瘤疫苗同其它免疫疗法的联合应用有可能成为肿瘤治疗领域的未来方向。然而,肿瘤疫苗的发展历经重重困难,但也积累了宝贵的临床研发经验。本文主要就不同类型治疗性肿瘤疫苗的起源、类型、作用机制及其优势与局限性展开论述,以期为今后肿瘤疫苗的研究工作提供帮助。

Therapeutic Tumor Vaccines: Past, Present and Future

Abstract


Tumor is a neoplasm due to abnormal cell proliferation under various tumorigenic factors. According to its biological characteristics and the degree of harm to the body, it is generally divided into benign and malignant types. In China, malignant tumor is one of the main causes of patient deaths, and its morbidity and mortality are constantly rising, which has become a very serious public health problem. Tumor vaccine is an immune intervention strategy that uses tumor-specific antigens or tumor-associated antigens to stimulate specific immune response to kill tumor cells. It is one of the hot topics in tumor immunotherapy research. In the past few decades, with the continuous development of genetic technology, the development of tumor vaccines has made great progress. Tumor vaccines have shown great potentials in preclinical studies and related trials on solid tumors andare expected to further improve the overall survival of patients. Tumor vaccine can be divided into preventive and therapeutic types. According to the underlying mechanism, tumor vaccines can be divided into cell vaccines, protein/synthetic peptide vaccines, nucleic acid vaccines, etc. At present, immuno-checkpoint inhibitors, adoptive cell therapy and nanomaterial-based immunotherapy have shown good efficacy in the treatment of cancer, and the combination of tumor vaccines and other immunotherapies may become the future direction in the field of cancer therapy. However, the development of tumor vaccines has experienced many difficulties. It also has accumulated valuable clinical research and development experiences. In this review, we mainly discuss the origin, type, mechanism, advantages and limitations of different types of therapeutic tumor vaccines, in order to provide a reference for the research in the future.

参考文献:

[1] McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future[J]. Cell, 2017,168(4):613-628
[2] Rusnock A A. Historical context and the roots of Jenner’s discovery[J]. Hum VaccinImmunother, 2016,12(8):2025-2028
[3] Coley W B. II.Contribution to the knowledge of sarcoma[J]. Ann Surg, 1891,14(3):199-220
[4] Hoover H C Jr, Surdyke M G, Dangel R B, et al. Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer[J]. Cancer, 1985,55(6):1236-1243
[5] van der Bruggen P, Traversari C, Chomez P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma[J].Science, 1991,254(5038):1643-1647
[6] Gardner T A, Elzey B D, Hahn N M. Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer[J].Hum VaccinImmunother, 2012,8(4):534-539
[7] Yang B, Jeang J, Yang A, et al. DNA vaccine for cancer immunotherapy[J]. Hum VaccinImmunother, 2014,10(11):3153-3164
[8] Mitchell D A, Batich K A, Gunn M D, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients[J]. Nature, 2015,519(7543):366-369
[9] Blass E, Ott P A. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines[J]. Nat Rev Clin Oncol, 2021,18(4):215-229
[10] Peng M, Mo Y, Wang Y, et al. Neoantigen vaccine: an emerging tumor immunotherapy[J]. Mol Cancer, 2019,18(1):128
[11] Hu Z, Leet DE, Allesøe RL, et al. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma[J]. Nat Med, 2021,27(3):515-525
[12] Ward E M, Flowers C R, Gansler T, et al. The importance of immunization in cancer prevention, treatment, and survivorship[J]. CA Cancer J Clin, 2017,67(5):398-410
[13] He Q, Gao H, Tan D, et al. mRNA cancer vaccines: advances, trends and challenges[J].Acta Pharm Sin B, 2022,12(7):2969-2989
[14] Berger M, Kreutz F T, Horst J L, et al. Phase I study with an autologous tumor cell vaccine for locally advanced or metastatic prostate cancer[J]. J Pharm Pharm Sci, 2007,10(2):144-152
[15] Schulof R S, Mai D, Nelson M A, et al. Active specific immunotherapy with an autologous tumor cell vaccine in patients with resected non-small cell lung cancer[J]. Mol Biother. 1988,1(1):30-36
[16] Asada H, Kishida T, Hirai H, et al. Significant antitumor effects obtained by autologous tumor cell vaccine engineered to secrete interleukin (IL)-12 and IL-18 by means of the EBV/lipoplex[J]. Mol Ther, 2002,5(5 Pt 1):609-616
[17] Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity[J]. Proc Natl Acad Sci U S A, 1993,90(8):3539-3543
[18] Fishman M, Hunter T B, Soliman H, et al. Phase II trial of B7-1 (CD-86) transduced, cultured autologous tumor cell vaccine plus subcutaneous interleukin-2 for treatment of stage IV renal cell carcinoma[J]. J Immunother, 2008,31(1):72-80
[19] Pulendran B, Ahmed R. Immunological mechanisms of vaccination[J]. Nat Immunol, 2011,12(6):509-517
[20] Melief C J, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines[J]. Nat Rev Cancer. 2008,8(5):351-360
[21] Chen X, Yang J, Wang L, et al. Personalized neoantigen vaccination with synthetic long peptides: recent advances and future perspectives[J]. Theranostics, 2020,10(13):6011-6023
[22] Rosalia R A, Quakkelaar E D, Redeker A, et al. Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation[J]. Eur J Immunol, 2013,43(10):2554-2565
[23] Liu L, Chen Q, Ruan C, et al.Platinum-based nanovectors engineered with immuno-modulating adjuvant for inhibiting tumor growth and promoting immunity[J]. Theranostics, 2018,8(11):2974-2987
[24] Liu J, Fu M, Wang M, et al. Cancer vaccines as promising immuno-therapeutics: platforms and current progress[J]. J Hematol Oncol, 2022,15(1):28
[25] Tang D C, DeVit M, Johnston S A. Genetic immunization is a simple method for eliciting an immune response[J]. Nature, 1992,356(6365):152-154
[26] McNeel D G, Becker J T, Eickhoff J C, et al. Real-time immune monitoring to guide plasmid DNA vaccination schedule targeting prostatic acid phosphatase in patients with castration-resistant prostate cancer[J]. Clin Cancer Res, 2014, 20(14): 3692-3704
[27] Trimble C L, Morrow M P, Kraynyak KA, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial[J]. Lancet, 2015,386(10008):2078-2088
[28] Weide B, Garbe C, Rammensee H G, et al. Plasmid DNA-and messenger RNA-based anti-cancer vaccination[J]. Immunol Lett, 2008,115(1):33-42
[29] Jackson N A C, Kester K E, Casimiro D, et al.The promise of mRNA vaccines: a biotech and industrial perspective[J]. NPJ Vaccines, 2020,5:11
[30] Pardi N, Hogan M J, Porter F W, et al. mRNA vaccines -a new era in vaccinology[J]. Nat Rev Drug Discov, 2018,17(4):261-279
[31] Vogel A B, Lambert L, Kinnear E, et al. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses[J]. Mol Ther, 2018,26(2):446-455
[32] Jou J, Harrington K J, Zocca M B, et al. The changing landscape of therapeutic cancer vaccines-novel platforms and neoantigen identification[J]. Clin Cancer Res, 2021,27(3):689-703
[33] Miao L, Zhang Y, Huang L. mRNA vaccine for cancer immunotherapy[J]. Mol Cancer, 2021,20(1):41
[34] Son S, Nam J, Zenkov I, et al. Sugar-nanocapsules imprinted with microbial molecular patterns for mRNA vaccination[J]. Nano Lett, 2020,20(3):1499-1509
[35] Jia L, Mao Y, Ji Q, et al. Decoding mRNA translatability and stability from the 5′ UTR[J].Nat Struct Mol Biol, 2020,27(9):814-821
[36] Hollingsworth R E, Jansen K. Turning the corner on therapeutic cancer vaccines[J]. NPJ Vaccines, 2019,4:7
[37] Warden C, Tang Q, Zhu H. Corrigendum to “herpesvirus BACs: past, present, and future”[J]. Biomed Res Int, 2019,2019:6870815
[38] Schlom J. Therapeutic cancer vaccines: current status and moving forward[J]. J Natl Cancer Inst, 2012,104(8):599-613
[39] Wang M, Zhao J, Zhang L, et al. Role of tumor microenvironment in tumorigenesis[J]. J Cancer, 2017,8(5):761-773
[40] Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future[J]. J Clin Invest, 2015,125(9):3384-3391
[41] Jiang X, Wang J, Deng X, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape[J]. Mol Cancer, 2019,18(1):10
[42] Ali O A, Lewin S A, Dranoff G, et al. Vaccines combined with immune checkpoint antibodies promote cytotoxic T-cell activity and tumor eradication[J]. Cancer Immunol Res, 2016,4(2):95-100
[43] Ott PA, Hu-Lieskovan S, Chmielowski B, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer[J]. Cell, 2020,183(2):347-362.e24
[44] Salvatori E, Lione L, Compagnone M, et al. Neoantigen cancer vaccine augments anti-CTLA-4 efficacy[J]. NPJ Vaccines, 2022,7(1):15
[45] Ma L, Dichwalkar T, Chang J Y H, et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor[J]. Science, 2019,365(6449):162-168
[46] Crosby EJ, Acharya CR, Haddad AF, et al. Stimulation of oncogene-specific tumor-infiltrating T cells through combined vaccine and αPD-1 enable sustained antitumor responses against established HER2 breast cancer[J]. Clin Cancer Res, 2020,26(17): 4670-4681
[47] Zhong R, Ling X, Cao S, et al. Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers[J]. ESMO Open, 2022,7(1):100334
[48] Fan Y, Kuai R, Xu Y, et al. Immunogenic cell death amplified by co-localized adjuvant delivery for cancer immunotherapy[J]. Nano Lett, 2017,17(12):7387-7393
[49] Gu Y Z, Fan C W, Lu R, et al. Forced co-expression of IL-21 and IL-7 in whole-cell cancer vaccines promotes antitumor immunity[J]. Sci Rep, 2016,6:32351
[50] Srinivasan P, Wu X, Basu M, et al. PD-L1 checkpoint inhibition and anti-CTLA-4 whole tumor cell vaccination counter adaptive immune resistance: a mouse neuroblastoma model that mimics human disease[J]. PLoS Med, 2018,15(1):e1002497
[51] Igarashi Y, Sasada T. Cancer vaccines: toward the next breakthrough in cancer immunotherapy[J]. J Immunol Res, 2020,2020:5825401
[52] Wculek S K, Cueto F J, Mujal A M, et al. Dendritic cells in cancer immunology and immunotherapy[J]. Nat Rev Immunol, 2020,20(1):7-24
[53] Roudko V, Greenbaum B, Bhardwaj N. Computational prediction and validation of tumor-associated neoantigens[J]. Front Immunol, 2020,11:27
[54] Jorritsma S H T, Gowans E J, Grubor-Bauk B, et al. Delivery methods to increase cellular uptake and immunogenicity of DNA vaccines[J]. Vaccine, 2016,34(46):5488-5494
[55] Diken M, Kranz L M, Kreiter S, et al. mRNA: a versatile molecule for cancer vaccines[J]. Curr Issues Mol Biol, 2017,22:113-128
[56] Hollingsworth R E, Jansen K. Turning the corner on therapeutic cancer vaccines[J]. NPJ Vaccines, 2019,4:7
[57] Foy S P, Mandl S J, dela Cruz T, et al. Poxvirus-based active immunotherapy synergizes with CTLA-4 blockade to increase survival in a murine tumor model by improving the magnitude and quality of cytotoxic T cells[J]. Cancer Immunol Immunother, 2016,65(5):537-549
[58] 卢岩,范云满,杨潇逸,等.全球肿瘤疫苗临床转化现状分析[J].中国药业(Lu Y, Fan YM, Yang XY, et al. Worldwide status of clinical translation in the field of tumor vaccines[J]. China Pharm),2021,20(22):10-15
[59] Berd D. M-Vax: an autologous, hapten-modified vaccine for human cancer[J].Expert Rev Vaccines, 2004,3(5):521-527
[60] Handy CE, Antonarakis ES. Sipuleucel-T for the treatment of prostate cancer: novel insights and future directions[J].Future Oncol, 2018,14(10):907-917
[61] Combe P, de Guillebon E, Thibault C, et al. Trial watch: therapeutic vaccines in metastatic renal cell carcinoma[J].Oncoimmunology, 2015,4(5): e1001236
[62] 秦岚群,邹征云.个体化肿瘤疫苗用于黑色素瘤治疗的研究进展[J].中国癌症杂志(Qin LQ, Zou ZY. Advances in personalized tumor vaccine for malignant melanoma[J]. China Oncol),2019,29(11):906-909
[63] Fishman M. A changing world for DCvax: a PSMA loaded autologous dendritic cell vaccine for prostate cancer[J].Expert Opin Biol Ther,2009,9(12):1565-1575
[64] Uyl-de Groot CA, Vermorken JB, Hanna MG Jr, et al. Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits[J].Vaccine, 2005,23(17-18):2379-2387
[65] Katsuda M, Miyazawa M, Ojima T, et al. A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy[J].Trials, 2019,20(1):242
[66] 郑树法. 高免疫原性人多形性胶质母细胞瘤U251细胞疫苗的研制及其诱导的体外抗瘤作用机制初探[D].福建医科大学(Zheng SF.The manufacture of human glioblastoma multiforme U251 cell vaccine with high immunogenicity and the probe of the mechanism of its antitumor in vitro[D].Fujian Medical University),2005
[67] 王玉名,张晓晶,邢浩.树突状细胞疫苗对黑色素瘤患者免疫功能的影响[J].医学与哲学(B) (Wang YM, Zhang XJ, Xing H. Study of dendritic cell vaccine on the immunologic function in patients with malignant melanoma[J]Med Philos B),2016,37(7):50-52
[68] Aris M, Bravo AI, Garcia Alvarez HM, et al. Immunization with the CSF-470 vaccine plus BCG and rhGM-CSF induced in a cutaneous melanoma patient a TCRβ repertoire found at vaccination site and tumor infiltrating lymphocytes that persisted in blood[J].Front Immunol,2019,10:2213
[69] 杜海洲.国际治疗性肿瘤疫苗的开发与研究进展[J].药学进展(Du HZ.Progress in international research and development of therapeutic cancer vaccine[J].Prog Pharm Sci),2018,42(9):685-696
[70] 马晓良,梅敬威,徐佳鸣.树突状细胞相关胶质母细胞瘤免疫治疗研究进展[J].沈阳医学院学报 (Ma XL, Mei JC, Xu JM.Progress in immunotherapy of dendritic cell-related glioblastoma[J].J Shenyang Med Coll),2022,24(4):427-431
[71] Wood CG, Mulders P. Vitespen: a preclinical and clinical review[J].Future Oncol, 2009,5(6):763-774
[72] 陈若冰,陈涛.疫苗在肺癌治疗中的研究进展[J].中国全科医学 (Chen RB, Chen T. Research progress of vaccines in the treatment of lung cancer[J].Chin Gen Pract), 2018, 21(23):2777-2780
[73] Gastrin 17 vaccine--Aphton: Anti-gastrin 17 immunogen, G17DT[J].BioDrugs,2003,17(3):223-225
[74] Slingluff CL, Lewis KD, Andtbacka R, et al. Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence[J].J Immunother Cancer, 2021,9(10): e003272
[75] Schneble EJ, Berry JS, Trappey FA, et al. The HER2 peptide nelipepimut-S (E75) vaccine (NeuVax?) in breast cancer patients at risk for recurrence: correlation of immunologic data with clinical response[J].Immunotherapy,2014,6(5):519-531
[76] Jain A G, Talati C, Pinilla-Ibarz J. Galinpepimut-S (GPS): an investigational agent for the treatment of acute myeloid leukemia[J]. Expert OpinInvestig Drugs, 2021,30(6): 595-601
[77] Pietragalla A, Duranti S, Daniele G, et al. Oregovomab: an investigational agent for the treatment of advanced ovarian cancer[J].Expert OpinInvestig Drugs, 2021,30(2):103-110
[78] Noguchi M, Arai G, Egawa S, et al. Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: a randomized phase II trial[J].Cancer Immunol Immunother, 2020,69(5):847-857
[79] Arlen PM, Gulley JL, Todd N, et al. Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer[J].J Urol, 2005,174(2):539-546
[80] Daiko H, Marafioti T, Fujiwara T, et al. Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients[J].Cancer Immunol Immunother,2020,69(11):2247-2257
[81] Chudasama R, Phung Q, Hsu A, et al. Vaccines in gastrointestinal malignancies: from prevention to treatment[J].Vaccines (Basel), 2021,9(6):647
[82] Cai S, Tan X, Miao K, et al. Effectiveness and safety of therapeutic vaccines for precancerous cervical lesions: a systematic review and meta-analysis[J].Front Oncol, 2022,12:918331
[83] Tarakanovskaya MG, Chinburen J, Batchuluun P, et al. Open-label Phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L[J].J Hepatocell Carcinoma,2017,4:59-69

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