中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

胰腺癌的免疫治疗

阮润生 徐克成

引用本文:
Citation:

胰腺癌的免疫治疗

详细信息
  • 中图分类号: R735.9

Immunotherapy of pancreatic cancer

  • 摘要: <正>胰腺癌迄今仍是一种最难治疗的恶性肿瘤。临床被诊断为胰腺癌的病人大约只有10%可以外科切除[1],然而,30年来胰腺癌的预后基本没有改善,总体5年生存率仍维持在<5%[2]。肿瘤局限于胰腺的病人平均生存期为6~10个月,一旦转移则只有3~6个月的生存期[3]。长期以来,5-FU一直作为一种首选的治疗胰腺癌的化疗药物。自1997三期临床试验结果报告

     

  • [1]Sultana A, Smith C Tudur, Cunningham D, et al.Systmatic re-view, including meta analysis, on the management of locally ad-vanced pancreatic cancer using radiation/combined modality therapy[J].Br J Cancer, 2007, 96 (8) ∶1183-1190.
    [2]Jemal A, Siegel R, Ward E, et al.Cancer statistics, 2008[J]. CA Cancer J Clin, 2008, 58 (2) ∶71-96.
    [3]Johnson CD.Guidelines for the management of patients with pancre-atic cancer periampullary and ampullary carcinomas[J].Gut, 2005, 54 (suppl5) ∶v1-16.
    [4]Burris HA3rd, Moore MJ, Andersen J, et al.Improvements in sur-vival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer:a randomized trial[J].J Clin Oncol, 1997, 15 (6) ∶2403-2413.
    [5]SultanaA, SmithCT, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer[J]. J Clin Oncol, 2007, 25 (18) ∶2607-2615.
    [6]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer[J]. Gut, 2007, 56 (8) ∶1134-1152.
    [7]Taipale J, Beachy PA.The Hedgehog and Wnt signaling pathways in cancer[J]. Nature, 2001, 411 (6835) ∶349-354.
    [8]Tseng JF, Farnebo FA, Kisker O, et al.Adenovirus-mediated de-livery of a soluble form of the VEGF receptor Flk1delays the growthof murine and human pancreatic adenocarcinoma in mice[J].Sur-gery, 2002, 132 (5) ∶857-865.
    [9]Kim D. Replication-selective oncolytic adenoviruses: virotherapy aimed at genetic targets in cancer[J]. Oncogene, 2000, 19 (56) ∶6660-6669.
    [10]Lindenmann J, Klein PA. viral oncolysis: increased imunogeniciy of host cell antigen associated with influenza virus[J]. J Exp Med, 1967, 126 (1) ∶93-108.
    [11]Shankaran V, Ikeda H, Bruce AT, et al.IFNgamma and lympho-cytes prevent primary tumour development and shape tumour immu-nogenicity[J].Nature, 2001, 410 (6832) ∶1107-1111.
    [12]Philip PA, Benedetti J, Fenoglio-Preiser C, et al.Phase III study of gemcitabine[G]pluscetuximab[C]versus gemcitabine in pa-tients[pts]with locally advanced or metastatic pancreatic adeno-carcinoma[PC]:SWOG S0205study[J].J Clin Oncol (Meeting abstracts) , 2007, 25 (18s) ∶LBA4509.
    [13]Krempien R, Munter MW, Timke C, et al.Cetuximab in combina-tion with intensity modulated radiotherapy (IMRI) and gemcitabine for patients with locally advanced pancreatic cancer:A prospective phase II trial[PARC-Study ISRCTN56652283][J].J Clin On-col (Meeting Abstracts) , 2007, 25 (suppl18) ∶4573.
    [14]Bangard C, Gossmann A, Papyan A, et al.Magnetic resonance im-aging in an orthotopic rat model:blockade of epidermal growth fac-tor receptor with EMD72000inhibits human pancreatic carcinoma growth[J].Int J Cancer, 2005, 114 (1) ∶131-138.
    [15]Graeven U, Kremer B, Sudhoff T, et al.Phase I study of the hu-manized anti-EGFR monoclonal antibody matuzumab (EMD72000) combined with gemcitabine in advanced pancreatic cancer[J].Br J Cancer, 2006, 94 (9) ∶1293-1299.
    [16]Kindler HL, Friberg G, Singh DA, et al.Phase II trial of bevaci-zumab plus gemcitabine in patients with advanced pancreatic cancer[J].J Clin Oncol, 2005, 23 (31) ∶8033-8040.
    [17]Bruckner HW, Hrehorovich VR, Sawhney HS.Bevacizumab as treatment for chemotherapy-resistant pancreatic cancer[J].Anti-cancer Res, 2005, 25 (5) ∶3637-3639.
    [18]Yamasaki H, Ikeda S, Okajima M, et al.Expression and localiza-tion of MUC1, MUC2, MUC5A and small intestinal mucin antigen in pancreatic tumors[J].Int J Oncol, 2004, 24 (1) ∶107-113.
    [19]Qu CF, Li Y, Song YJ, et al. MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213) Bi-C595 radioimmunoconjugate[J]. Br J Cancer, 2004, 91 (12) ∶2086-2093.
    [20]Levi E, Klimstra DS, Andea A, et al.MUC1and MUC2in pancre-atic neoplasia[J].J Clin Pathol, 2004, 57 (5) ∶456-462.
    [21]Hamanaka Y, Suehiro Y, Fukui M, et al. Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cnacer[J]. Int J Cancer, 2003, 103 (1) ∶97-100.
    [22]Tsutsumida H, Swanson BJ, Singh PK, et al.RNA interference suppression of MUC1reduces the growth rate and metastatic pheno-type of human pancreatic cancer cells[J].Clin Cancer Res, 2006, 12 (10) ∶2976-2987.
    [23]Gold DV, Modrak DE, Schutsky K, et al.Combined90Yttrium-DOTA-labeled PAM4antibody radioimmunotherapy and gemcit-abine radiosensitization for the treatment of a human pancreatic cancer xenograft[J].Int J Cance, 2004, 109 (4) ∶618-626.
    [24]Hassan R, Bera T, Pastan I.Mesothelin:a new target for immuno-therapy[J].Clin Cancer Res, 2004, 10 (12Pt1) ∶3937-3942.
    [25]Argani P, Iacobuzio-Donahue C, Ryu B, et al. Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE) [J]. Clin Cancer Res, 2001, 7 (12) ∶3862-3868.
    [26]Hassan R, Laszik ZG, Lerner M, et al. Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis[J]. Am J Clin Pathol, 2005, 124 (6) ∶838-845.
    [27]Baruch AC, Wang H, Staeket GA, et al.Immunocytochemical study of the expression of mesothelin in fine-needle aspiration bi-opsy specimens of pancreatic adenocarcinoma[J].Diagn Cyto-pathol, 2007, 35 (3) ∶143-147.
    [28]Li M, Bharadwaj U, Zhang R, et al.Mesothilin is a malignant fac-tor and therapeutic vaccine target for pancreatic cancer[J].MolCa-ncer Ther, 2008, 7 (2) ∶286-296.
    [29]Armstrong DK, Laheru D, Ma WW, et al.A phase I study of MORAb-009, a monoclonal antibody against mesothelin in pan-creatic cancer, Mesothelioma and ovarian adenocarcinoma[J].J Clin Oncol (Meeting Abstracts) , 2007, 25 (suppl18) ∶14041.
    [30]Loo D, Pryer N, Young P, et al.The glycotope-specific RAV12monoclonal antibody induces oncosis in vitro and has antitumor ac-tivity against gastrointestinal adenocarcinoma tumor xenografts in vi-vo[J].Mol Cancer Ther, 2007, 6 (3) ∶856-865.
    [31]Burris HA III, Lewis N, Rosen LS, et al.Phase I experience with an anti-glycotope monoclonal antibody, RAV12, in recurrent ade-nocarcinoma[J].J Clin Oncol (Meeting Abstracts) , 2007, 25 (suppl18) ∶14017.
    [32]Kobari M, Egawa S, Shibuya K, et al. Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer[J]. Br J Surg, 2000, 87 (1) ∶43-48.
    [33]Hahn WC. Role of telomeres and telomerase in the pathogenesis of human cancer[J]. J Clin Oncol, 2003, 21 (10) ∶2034-2043.
    [34]HiyamaE, Kodama T, Shinbara K, et al.Telomerase activity is de-tected in pancreatic cancer but not in benign tumors[J].Cancer Res, 1997, 57 (2) ∶326-331.
    [35]Myung SJ, Kim MH, Kim YS, et al.Telomerase activity in pure pancreatic juice for the diagnosis of pancreatic cancer may be com-plementary to K-ras mutation[J].Gastrointest Endosc, 2000, 51 (6) ∶708-713.
    [36]Sato N, Maehara N, Mizumoto K, et al.Telomerase activity of cul-tured human pancreatic carcinoma cell lines correlates with their po-tential for migration and invasion[J].Cancer, 2001, 91 (3) ∶496-504.
    [37]Tang SJ, Dumot JA, Wang L, et al.Telomerase activity in pancre-atic endocrine tumors[J].Am J Gastroenterol, 2002, 97 (4) ∶1022-1030.
    [38]Sato N, Mizumoto K, Kusumoto M, et al.Up-regulation of telom-erase activity in human pancreatic cancer cells after exposure to eto-poside[J].Br J Cancer, 2000, 82 (11) ∶1819-1826.
    [39]Schmidt J, Ryschich E, Sievers E, et al. Telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo[J]. Cancer, 2006, 106 (4) ∶759-764.
    [40]Mukherjee P, Ginardi AR, Madsen CS, et al.Mice with spontane-ous pancreatic cancer naturally develop MUC-1-specific CTLs that eradicate tumors when adoptively transferred[J].J Immunol, 2000, 165 (6) ∶3451-3460.
    [41]Kawakami Y, Okada T, Akada M. Development of immunotherapy for pancreatic cancer[J]. Pancreas, 2004, 28 (3) ∶320-325.
    [42]Yamaguchi Y, Ohta K, Kawabuchi Y, et al.Feasibility study of a-doptive immunotherapy formetastatic lung tumors using peptide-pulsed dendritic cell-activated killer (PDAK) cells[J].Antican-cer Res, 2005, 25 (3c) ∶2407-2415.
    [43]Jaffee Em, Hruban RH, Biedrzycki B, et al.Novel allogeneic gran-ulocyte-macrophage colony-stimulating factor-secreting tumor waccine for pancreatic cancer:a phase I trial of safety and immune activation[J].J Clin Oncol, 2001, 19 (1) ∶145-156.
    [44]Laheru D, Yeo C, Biedrycki B, et al.A safety and efficacy trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene in combination with adjuvant chemoradiotherapy for the treatment of adenocarcinoma of the pancreas[J].J Clin On-col (Meeting Abstracts) , 2007, 25 (suppl18) ∶3010.
    [45]Almoguera C, Shibata D, Forrester K, et al.Most human carcino-mas of the exocrine pancreas contain mutant C-K-ras gens[J].Cell, 1988, 53 (4) ∶549-554.
    [46]Malumbres M, Barbacid M. RAS oncogenes: the first 30 years[J]. Nat Rev Cancer, 2003, 3 (6) ∶459-465.
    [47]Luttges J, Schlehe B, Menke MA, et al.The K-ras mutation pat-tern in pancreatic ductal adenocarcinoma usually is identical to that in asscociated normal, hyperplastic, and metaplastic ductal epithe-lium[J].Cancer, 1999, 85 (8) ∶1703-1710.
    [48]Toubaji A, Achtar MS, Herrin VE, et al. Immunotherapeutic role of mutant ras peptide-based vaccine as an adjuvant in pancreatic and colorectal cancer[J]. J Clin Oncol (Meeting Abstracts) , 2005, 23 (suppl 16) ∶2573.
    [49]Gjertsen MK, Bakka A, Brivik J, et al.Ex vivo ras peptide vacci-nation in patients with advanced pancreatic cancer:results of a phase I/II study[J].Int J Cancer, 1996, 65 (4) ∶450-453.
    [50]Gjertsen MK, Buanes T, Rosseland AR, et al.Intrdermal ras pep-tide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant:Clinical and innunological responses in patients with pancreatic adenocarcinoma[J].Int J Cancer, 2001, 92 (3) ∶441-450.
    [51]Achtar MS, Toubaji A, Herrin V, et al.Phase II clinical trial of mutant Ras peptide vaccine in combinationwith GM-CSF and IL-2in advanced cancer patients[J].J Clin Oncol (Meeting Ab-stracts) , 2007, 25 (suppl18) ∶3067.
    [52]Buanes T, Bernhardt S, Lislerud K, et al.RAS peptide vaccination in resected pancreatic cancer patients-persistence of anti tumour response and long tern survival[J].J Clin Oncol (Meeting Ab-stracts) , 2007, 25 (suppl18) ∶4543.
    [53]Lieberman SM, Horig H, Kaufman HL. Innovative treatments for pancreatic cancer[J]. Surg Clin North Am, 2001, 81 (3) ∶715-739.
    [54]Duraker N, Hot S, Polat Y, et al.CEA, CA19-9and CA125in the differential diagnosis of benign and malignant pancreatic disea-ses with or without jaundice[J].J Surg Oncol, 2007, 95 (2) ∶142-147.
    [55]Ozkan H, kaya M, Gengiz A. Comparison of tumor marker CA 242 with CA 19-9 and carcinoembryonic antigen (CEA) in pancreatic cancer[J]. Hepatogastroenterology, 2003, 50 (53) ∶1669-1674.
    [56]Banfi G, Bravi S, Ardemagni A, et al. CA 19.9, CA 242 and CEA in the diagnosis and follow-up of pancreatic cancer[J]. Int J Biol Markers, 1996, 11 (2) ∶77-81.
    [57]Marshall JL, Hawkins MJ, Tsang KY, et al.Phase I study in canc-er patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen[J].J Clin Oncol, 1999, 17 (1) ∶332.
    [58]Nordqvist C. Therion reports results of phase 3 PANVAC-VF trial and announces plans for company sale[N]. Medical News Today, 2006-06-29.
    [59]Brett BT, Smith SC, Bouvier CV, et al. Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer[J]. J Clin Oncol, 2002, 20 (20) ∶4225-4231.
    [60]Gilliam AD, Topuzov EG, Garin AM, et al.Randomised, double blind, placebo-controlled, multi-centre, group-sequential trial of G17DT for patients with advanced pancreatic cancer unsuitable or unwilling to take chemotherapy[J].J Clin Oncol (Meeting Ab-stracts) , 2004, 22 (suppl14) ∶2511.
    [61]Shapiro J, Marshall J, Karasek P, et al.G17DT+gemcitabine[Gem]versus placebo+Gem in untreated subjects with locally ad-vanced, recurrent, or metastatic adenocarcinoma of the pancreas:Results of a randomized, double-blind, multinational, multicenter study[J].J Clin Oncol (Meeting Abstracts) , 2005, 23 (suppl16) ∶LBA4012.
    [62]Thomas AM, Santarsienro lm, Lutz ER, et al.Mesothelin-specific CD8 (+) T cell responses provide evidence of in vivo cross-prim-ing by antigen-presenting cells in vaccinated pancreatic cancer pa-tients[J].J Exp Med, 2004, 200 (3) ∶297-306.
    [63]Gaffney MC, Goedegebuure P, Kashiwagi H, et al.DNA vaccina-tion targeting mesothelin combined with anti-GITR antibody in-duces rejection of pancreatic adenocarcinoma[J].AACR Meeting Abstracts, 2006, 2006 (47) ∶329-a.
    [64]Cohen AD, Diab A, Perales MA, et al.Agonist anti-GITR anti-body enhances vaccine-induced CD8 (+) T-cell responses and tumor immunity[J].Cancer Res, 2006, 66 (9) ∶4904-4912.
    [65]Esparza EM, Arch RH. Glucocorticoid-induced TNF receptor functions as a costimulatory receptor that promotes survival in early phases of T cell activation[J]. J Immunol, 2005, 174 (12) ∶7869-7874.
    [66]Bernhardt SL, Gjertsen MK, Trachsel S, et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer. A dose escalating phase I/II study[J]. Br J Cancer, 2006, 95 (11) ∶1474-1482.
    [67]Miyazaki J, Tsuzuki Y, Matsuzaki K, et al. Combination therapy with tumor-lysate pulsed dendritic cells and antiangiogenic drug TNP-470 for mouse pancreatic cancer[J]. Int J Cancer, 2005, 117 (3) ∶499-505.
    [68]Morse MA, Nair SK, Boczkowski D, et al.The feasibility and safe-ty of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer[J].Int J Gastrointest Cancer, 2002, 32 (1) ∶1-6.
    [69]Pecher G, Haring A, Kaiser L, et al.Mucin gene (MUC1) trans-fered dendritic cells as vaccine:results of a phase I/II clinical trial[J].Cancer Immunol Immunother, 2002, 51 (11-12) ∶669-673.
    [70]Finn OJ, Whiteside T, McKolanis J, et al. A phase IB study of a MUC1 pulsed autologous dendritic cell (DC) vaccine as adjuvant therapy in patients (Pts) with resected pancreatic or biliary tumors[J]. J Clin Oncol (Meeting Abstracts) , 2004, 22 (suppl 14) ∶2578.
    [71]News and Analysis. Rethinking therapeutic cancer vaccines[J]. Nat Rev Durg Discov, 2009, 8 (9) ∶685-686.
  • 加载中
计量
  • 文章访问数:  2406
  • HTML全文浏览量:  17
  • PDF下载量:  720
  • 被引次数: 0
出版历程
  • 出版日期:  2010-05-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回