Review

† Author for correspondence

Email the corresponding author at lfriend@wustl.edu

Washington University School of Medicine, Department of Surgery, 660 S. Euclid Avenue, Box 8109, Saint Louis MO 63110, USA

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Peter Goedegebuure

Washington University School of Medicine, Department of Surgery, 660 S. Euclid Avenue, Box 8109, Saint Louis MO 63110, USA

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Published Online:4 Apr 2011https://doi.org/10.2217/imt.11.10

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Abstract

Pancreatic adenocarcinoma is the fourth leading cause of cancer death with an overall 5-year survival of less than 5%. As there is ample evidence that pancreatic adenocarcinomas elicit antitumor immune responses, identification of pancreatic cancer-associated antigens has spurred the development of vaccination-based strategies for treatment. While promising results have been observed in animal tumor models, most clinical studies have found only limited success. As most trials were performed in patients with advanced pancreatic cancer, the contribution of immune suppressor mechanisms should be taken into account. In this article, we detail recent work in tumor antigen vaccination and the recently identified mechanisms of immune suppression in pancreatic cancer. We offer our perspective on how to increase the clinical efficacy of vaccines for pancreatic cancer.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

1 Jemal A, Siegel R, Xu J, Ward E: Cancer statistics. CA Cancer J. Clin.60(5),277–300 (2010).
MedlineGoogle Scholar
2 Cress RD, Yin D, Clarke L, Bold R, Holly EA: Survival among patients with adenocarcinoma of the pancreas: a population-based study (United States). Cancer Causes Control17(4),403–409 (2006).
MedlineGoogle Scholar
3 Winter JM, Cameron JL, Campbell KA et al.: 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J. Gastrointest. Surg.10(9),1199–1210 (2006).
MedlineGoogle Scholar
4 Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP: Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. J. Oncol. Pract.9(2),99–132 (2008).
Google Scholar
5 Roy R, Maraveyas A: Chemoradiation in pancreatic adenocarcinoma: a literature review. Oncologist15(3),259–269 (2010).
Medline CASGoogle Scholar
6 Mackenzie RP, McCollum AD: Novel agents for the treatment of adenocarcinoma of the pancreas. Expert Rev. Anticancer Ther.9(10),1473–1485 (2009).
MedlineGoogle Scholar
7 Goldman B, DeFrancesco L: The cancer vaccine roller coaster. Nat. Biotechnol.27(2),129–139 (2009).
Medline CASGoogle Scholar
8 Yokokawa J, Palena C, Arlen P et al.: Identification of novel human CTL epitopes and their agonist epitopes of mesothelin. Clin. Cancer Res.11(17),6342–6351 (2005).
Medline CASGoogle Scholar
9 Andersen MH, Pedersen LO, Becker JC, Straten PT: Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients. Cancer Res.161(3),869–872 (2001).
Google Scholar
10 Johnston FM, Tan MC, Tan BR Jr et al.: Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. Clin. Cancer Res.15(21),6511–6518 (2009).
Medline CASGoogle Scholar
11 Kotera Y, Fontenot JD, Pecher G, Metzgar RS, Finn OJ: Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients. Cancer Res.54(11),2856–2860 (1994).
Medline CASGoogle Scholar
12 Kubuschok B, Neumann F, Breit R et al.: Naturally occurring T-cell response against mutated p21 ras oncoprotein in pancreatic cancer. Clin. Cancer Res.12(4),1365–1372 (2006).
Medline CASGoogle Scholar
13 Wenandy L, Sorensen RB, Sengelov L, Svane IM, Thor SP, Andersen MH: The immunogenicity of the hTERT540–548 peptide in cancer. Clin. Cancer Res.14(1),4–7 (2008).
Medline CASGoogle Scholar
14 Yanagimoto H, Mine T, Yamamoto K et al.: Immunological evaluation of personalized peptide vaccination with gemcitabine for pancreatic cancer. Cancer Sci.98(4),605–611 (2007).
Medline CASGoogle Scholar
15 Dunn GP, Koebel CM, Schreiber RD: Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol.6(11),836–848 (2006).▪▪ Summarizes the evidence for immune surveillance of cancer, in particular through interferons, and offers a model for how tumors escape from immune recognition.
Medline CASGoogle Scholar
16 Swann JB, Smyth MJ: Immune surveillance of tumors. J. Clin. Invest.117(5),1137–1146 (2007).
Medline CASGoogle Scholar
17 Hamanaka Y, Suehiro Y, Fukui M, Shikichi K, Imai K, Hinoda Y: Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer. Int. J. Cancer103(1),97–100 (2003).
Medline CASGoogle Scholar
18 Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH: Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene29(8),1093–1102 (2010).
Medline CASGoogle Scholar
19 Clark CE, Beatty GL, Vonderheide RH: Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett.279(1),1–7 (2009).
Medline CASGoogle Scholar
20 Fong L, Small EJ: Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J. Clin. Oncol.26(32),5275–5283 (2008).
Medline CASGoogle Scholar
21 Paulos CM, June CH: Putting the brakes on BTLA in T cell-mediated cancer immunotherapy. J. Clin. Invest.120(1),76–80 (2010).
Medline CASGoogle Scholar
22 Pardoll D: Does the immune system see tumors as foreign or self? Annu. Rev. Immunol.21,807–839 (2003).
Medline CASGoogle Scholar
23 Ikemoto T, Yamaguchi T, Morine Y et al.: Clinical roles of increased populations of Foxp3⁺CD4⁺ T cells in peripheral blood from advanced pancreatic cancer patients. Pancreas33(4),386–390 (2006).
MedlineGoogle Scholar
24 Hiraoka N, Onozato K, Kosuge T, Hirohashi S: Prevalence of FOXP3⁺ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin. Cancer Res.12(18),5423–5434 (2006).
Medline CASGoogle Scholar
25 Nomi T, Sho M, Akahori T et al.: Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin. Cancer Res.13(7),2151–2157 (2007).
Medline CASGoogle Scholar
26 Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science299(5609),1057–1061 (2003).
Medline CASGoogle Scholar
27 Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol.155(3),1151–1164 (1995).▪▪ The first description of Treg cells as regulators of autoimmunity.
Medline CASGoogle Scholar
28 Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4⁺CD25⁺ regulatory T cells. Nat. Immunol.4(4),330–336 (2003).
Medline CASGoogle Scholar
29 Khattri R, Cox T, Yasayko SA, Ramsdell F: An essential role for Scurfin in CD4⁺CD25⁺ T regulatory cells. Nat. Immunol.4(4),337–342 (2003).
Medline CASGoogle Scholar
30 Linehan DC, Goedegebuure PS: CD25⁺ CD4⁺ regulatory T-cells in cancer. Immunol. Res.32(1–3),155–168 (2005).
Medline CASGoogle Scholar
31 van der Bruggen P, Traversari C, Chomez P et al.: A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science254(5038),1643–1647 (1991).▪▪ The first paper describing the molecular identification of a human tumor antigen recognized by cytolytic T cells.
Medline CASGoogle Scholar
32 Peoples GE: HER2 vaccination in high-risk breast cancer. Clin. Adv. Hematol. Oncol.7(11),715–717 (2009).
MedlineGoogle Scholar
33 Weden S, Klemp M, Gladhaug IP et al.: Long term follow-up of resected pancreatic cancer patients following vaccination against mutant K-RAS. Int. J. Cancer12 (2010).▪ Provides evidence that vaccination against mutated K-Ras peptides offers long-term protection against recurrence in some patients with pancreatic cancer.
Google Scholar
34 Hensler T, Hecker H, Heeg K et al.: Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect. Immun.65(6),2283–2291 (1997).
Medline CASGoogle Scholar
35 Shakhar G, Ben-Eliyahu S: Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann. Surg. Oncol.10(8),972–992 (2003).
MedlineGoogle Scholar
36 Weighardt H, Heidecke CD, Emmanuilidis K et al.: Sepsis after major visceral surgery is associated with sustained and interferon-γ-resistant defects of monocyte cytokine production. Surgery127(3),309–315 (2000).
Medline CASGoogle Scholar
37 Saito H, Dubsky P, Dantin C, Finn OJ, Banchereau J, Palucka AK: Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8⁺ T cells by dendritic cells loaded with killed allogeneic breast cancer cells. Breast Cancer Res.8(6),R65 (2006).
MedlineGoogle Scholar
38 Thomas AM, Santarsiero LM, Lutz ER et al.: Mesothelin-specific CD8⁺ T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J. Exp. Med.200(3),297–306 (2004).
Medline CASGoogle Scholar
39 Jaffee EM, Hruban RH, Biedrzycki B et al.: Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a Phase I trial of safety and immune activation. J. Clin. Oncol.19(1),145–156 (2001).
Medline CASGoogle Scholar
40 Hassan R, Ho M: Mesothelin targeted cancer immunotherapy. Eur. J. Cancer44(1),46–53 (2008).
Medline CASGoogle Scholar
41 Beatson RE, Taylor-Papadimitriou J, Burchell JM: MUC1 immunotherapy. Immunotherapy2(3),305–327 (2010).
CASGoogle Scholar
42 Mandell RB, Flick R, Staplin WR et al.: The αGal HyperAcute^® technology: enhancing immunogenicity of antiviral vaccines by exploiting the natural αGal-mediated zoonotic blockade. Zoonoses Public Health56(6–7),391–406, (2009).
Medline CASGoogle Scholar
43 Macher BA, Galili U: The Galα1,3Galβ1,4GlcNAc-R (α-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim. Biophys. Acta1780(2),75–88 (2008).
Medline CASGoogle Scholar
44 Deguchi T, Tanemura M, Miyoshi E et al.: Increased immunogenicity of tumor-associated antigen, mucin 1, engineered to express α-Gal epitopes: a novel approach to immunotherapy in pancreatic cancer. Cancer Res.70,5259 (2010).
Medline CASGoogle Scholar
45 Rossi GR, Unfer RC, Seregina T, Link CJ: Complete protection against melanoma in absence of autoimmune depigmentation after rejection of melanoma cells expressing α(1,3)galactosyl epitopes. Cancer Immunol. Immunother.54(10),999–1009 (2005).
Medline CASGoogle Scholar
46 Rossi GR, Mautino MR, Awwad DZ et al.: Allogeneic melanoma vaccine expressing αGal epitopes induces antitumor immunity to autologous antigens in mice without signs of toxicity. J. Immunother.31(6),545–554 (2008).
Medline CASGoogle Scholar
47 Koido S, Hara E, Homma S et al.: Cancer vaccine by fusions of dendritic and cancer cells. Clin. Dev. Immunol.2009,657369 (2009).
MedlineGoogle Scholar
48 Schmidt T, Ziske C, Marten A et al.: Intratumoral immunization with tumor RNA-pulsed dendritic cells confers antitumor immunity in a C57BL/6 pancreatic murine tumor model. Cancer Res.63(24),8962–8967 (2003).
Medline CASGoogle Scholar
49 Kyte JA, Mu L, Aamdal S, Kvalheim G, Dueland S, Hauser M et al.: Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther.13(10),905–918 (2006).
Medline CASGoogle Scholar
50 Kyte JA, Kvalheim G, Lislerud K et al.: T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. Cancer Immunol. Immunother.56(5),659–675 (2007).
Medline CASGoogle Scholar
51 Schnurr M, Scholz C, Rothenfusser S et al.: Apoptotic pancreatic tumor cells are superior to cell lysates in promoting cross-priming of cytotoxic T cells and activate NK and γδ T cells. Cancer Res.62(8),2347–2352 (2002).
Medline CASGoogle Scholar
52 Kantoff PW, Higano CS, Shore ND et al.: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med.363(5),411–422 (2010).
Medline CASGoogle Scholar
53 Mazzolini G, Alfaro C, Sangro B et al.: Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J. Clin. Oncol.23(5),999–1010 (2005).
Medline CASGoogle Scholar
54 Koido S, Homma S, Hara E et al.: Antigen-specific polyclonal cytotoxic T lymphocytes induced by fusions of dendritic cells and tumor cells. J. Biomed. Biotechnol.752381 (2010).▪ Reviews on the use of dendritic cell–tumor cell fusions and their ability to induce antigen-specific T-cell responses.
MedlineGoogle Scholar
55 Yamamoto M, Kamigaki T, Yamashita K et al.: Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer. Oncol. Rep.22(2),337–343 (2009).
Medline CASGoogle Scholar
56 Pecher G, Haring A, Kaiser L, Thiel E: Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a Phase I/II clinical trial. Cancer Immunol. Immunother.51(11–12),669–673 (2002).
Medline CASGoogle Scholar
57 Lepisto AJ, Moser AJ, Zeh H et al.: A Phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors. Cancer Ther.6(B),955–964 (2008).
Medline CASGoogle Scholar
58 Aloysius MM, Mc Kechnie AJ, Robins RA et al.: Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs. J. Transl. Med.7,18 (2009).
MedlineGoogle Scholar
59 Carbone DP, Ciernik IF, Kelley MJ et al.: Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome. J. Clin. Oncol.23(22),5099–5107 (2005).
MedlineGoogle Scholar
60 Ramanathan RK, Lee KM, McKolanis J et al.: Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol. Immunother.54(3),254–264 (2005).
Medline CASGoogle Scholar
61 Yamamoto K, Ueno T, Kawaoka T et al.: MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer. Anticancer Res.25(5),3575–3579 (2005).
Medline CASGoogle Scholar
62 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. Br. J. Cancer95(11),1474–1482 (2006).
Medline CASGoogle Scholar
63 Buanes T, Maurel J, Liauw W, Hebbar M, Nemunaitis J: A randomized Phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable and metastatic pancreatic cancer (PC). J. Clin. Oncol.27(Suppl. 15), Abstract 4601 (2009).
Google Scholar
64 Miyazawa M, Ohsawa R, Tsunoda T et al.: Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci.101(2),433–439 (2010).
Medline CASGoogle Scholar
65 Toubaji A, Achtar M, Provenzano M et al.: Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. Cancer Immunol. Immunother.57(9),1413–1420 (2008).
Medline CASGoogle Scholar
66 Begley J, Ribas A: Targeted therapies to improve tumor immunotherapy. Clin. Cancer Res.14(14),4385–4391 (2008).
MedlineGoogle Scholar
67 Chapatte L, Ayyoub M, Morel S et al.: Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses. Cancer Res.1566(10),5461–5468 (2006).
Google Scholar
68 Houghton AN, Guevara-Patino JA: Immune recognition of self in immunity against cancer. J. Clin. Invest.114(4),468–471 (2004).
Medline CASGoogle Scholar
69 Weiner LM, Surana R, Murray J: Vaccine prevention of cancer: can endogenous antigens be targeted? Cancer Prev. Res. (Phila.)3(4),410–415 (2010).
Medline CASGoogle Scholar
70 Yu Z, Theoret MR, Touloukian CE et al.: Poor immunogenicity of a self/tumor antigen derives from peptide–MHC-I instability and is independent of tolerance. J. Clin. Invest.114(4),551–559 (2004).
Medline CASGoogle Scholar
71 Tsang KY, Palena C, Gulley J, Arlen P, Schlom J: A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1. Clin. Cancer Res.10(6),2139–2149 (2004).
Medline CASGoogle Scholar
72 Wobser M, Keikavoussi P, Kunzmann V, Weininger M, Andersen MH, Becker JC: Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin. Cancer Immunol. Immunother.55(10),1294–1298 (2006).▪ Clinical evidence that vaccination against a pancreas cancer-associated antigen can induce a protective immune response.
Medline CASGoogle Scholar
73 Charalambous A, Oks M, Nchinda G, Yamazaki S, Steinman RM: Dendritic cell targeting of survivin protein in a xenogeneic form elicits strong CD4⁺ T cell immunity to mouse survivin. J. Immunol.177(12),8410–8421 (2006).
Medline CASGoogle Scholar
74 Wang B, Kuroiwa JM, He LZ, Charalambous A, Keler T, Steinman RM: The human cancer antigen mesothelin is more efficiently presented to the mouse immune system when targeted to the DEC-205/CD205 receptor on dendritic cells. Ann. NY Acad. Sci.1174,6–17 (2009).
Medline CASGoogle Scholar
75 Shibagaki N, Udey MC: Dendritic cells transduced with protein antigens induce cytotoxic lymphocytes and elicit antitumor immunity. J. Immunol.168(5),2393–2401 (2002).
Medline CASGoogle Scholar
76 Bae MY, Cho NH, Seong SY: Protective anti-tumour immune responses by murine dendritic cells pulsed with recombinant Tat-carcinoembryonic antigen derived from Escherichia coli. Clin. Exp. Immunol.157(1),128–138 (2009).
Medline CASGoogle Scholar
77 Tanaka Y, Dowdy SF, Linehan DC, Eberlein TJ, Goedegebuure PS: Induction of antigen-specific CTL by recombinant HIV trans-activating fusion protein-pulsed human monocyte-derived dendritic cells. J. Immunol.170(3),1291–1298 (2003).
Medline CASGoogle Scholar
78 Viehl CT, Tanaka Y, Chen T et al.: Tat mammaglobin fusion protein transduced dendritic cells stimulate mammaglobin-specific CD4 and CD8 T cells. Breast Cancer Res. Treat.91(3),271–278 (2005).
Medline CASGoogle Scholar
79 Viehl CT, Becker-Hapak M, Lewis JS et al.: A Tat fusion protein-based tumor vaccine for breast cancer. Ann. Surg. Oncol.12(7),517–525 (2005).
MedlineGoogle Scholar
80 Saha A, Chatterjee SK, Foon KA, Bhattacharya-Chatterjee M: Anti-idiotype antibody induced cellular immunity in mice transgenic for human carcinoembryonic antigen. Immunology118(4),483–496 (2006).
Medline CASGoogle Scholar
81 Saha A, Baral RN, Chatterjee SK et al.: CpG oligonucleotides enhance the tumor antigen-specific immune response of an anti-idiotype antibody-based vaccine strategy in CEA transgenic mice. Cancer Immunol. Immunother.55(5),515–527 (2006).
MedlineGoogle Scholar
82 Saha A, Chatterjee SK, Foon KA, Celis E, Bhattacharya-Chatterjee M: Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA-A2 with a combination of anti-idiotype vaccine and CTL peptides of carcinoembryonic antigen. Cancer Res.67(6),2881–2892 (2007).
Medline CASGoogle Scholar
83 Yanagimoto H, Shiomi H, Satoi S et al.: A Phase II study of personalized peptide vaccination combined with gemcitabine for non-resectable pancreatic cancer patients. Oncol. Rep.24(3),795–801 (2010).
Medline CASGoogle Scholar
84 Bodles-Brakhop AM, Draghia-Akli R: DNA vaccination and gene therapy: optimization and delivery for cancer therapy. Expert Rev. Vaccines7(7),1085–1101 (2008).
Medline CASGoogle Scholar
85 Zhu K, Qin H, Cha SC et al.: Survivin DNA vaccine generated specific antitumor effects in pancreatic carcinoma and lymphoma mouse models. Vaccine25(46),7955–7961 (2007).
Medline CASGoogle Scholar
86 Rong Y, Jin D, Wu W et al.: Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine. BMC Cancer9,191 (2009).
MedlineGoogle Scholar
87 Chang CL, Wu TC, Hung CF: Control of human mesothelin-expressing tumors by DNA vaccines. Gene Ther.14(16),1189–1198 (2007).
Medline CASGoogle Scholar
88 Dong Y, Qian J, Ibrahim R, Berzofsky JA, Khleif SN: Identification of H-2Db-specific CD8⁺ T-cell epitopes from mouse VEGFR2 that can inhibit angiogenesis and tumor growth. J. Immunother.29(1),32–40 (2006).
Medline CASGoogle Scholar
89 Johansson S, Ek M, Wahren B, Stout R, Liu M, Hallermalm K: Intracellular targeting of CEA results in Th1-type antibody responses following intradermal genetic vaccination by a needle-free jet injection device. ScientificWorldJournal7,987–999 (2007).
Medline CASGoogle Scholar
90 Brave A, Hallengard D, Gudmundsdotter L et al.: Late administration of plasmid DNA by intradermal electroporation efficiently boosts DNA-primed T and B cell responses to carcinoembryonic antigen. Vaccine27(28),3692–3696 (2009).
Medline CASGoogle Scholar
91 Hallermalm K, Johansson S, Brave A et al.: Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer. Scand. J. Immunol.66(1),43–51 (2007).
Medline CASGoogle Scholar
92 Yu YY, Netuschil N, Lybarger L, Connolly JM, Hansen TH: Cutting edge: single-chain trimers of MHC class I molecules form stable structures that potently stimulate antigen-specific T cells and B cells. J. Immunol.168(7),3145–3149 (2002).
Medline CASGoogle Scholar
93 Huang CH, Peng S, He L et al.: Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope. Gene Ther.12(15),1180–1186 (2005).
Medline CASGoogle Scholar
94 Li L, Herndon JM, Truscott SM et al.: Engineering superior DNA vaccines: MHC class I single chain trimers bypass antigen processing and enhance the immune response to low affinity antigens. Vaccine2328(8),1911–1918 (2010).
Google Scholar
95 Zhang Y, Li S, Shan M et al.: Hepatitis B virus core antigen epitopes presented by HLA-A2 single-chain trimers induce functional epitope-specific CD8⁺ T-cell responses in HLA-A2.1/Kb transgenic mice. Immunology121(1),105–112 (2007).
Medline CASGoogle Scholar
96 Cheung YK, Cheng SC, Sin FW, Chan KT, Xie Y: Induction of T-cell response by a DNA vaccine encoding a novel HLA-A*0201 severe acute respiratory syndrome coronavirus epitope. Vaccine25(32),6070–6077 (2007).
Medline CASGoogle Scholar
97 Cheung YK, Cheng SC, Ke Y, Xie Y: Two novel HLA-A*0201 T-cell epitopes in avian H5N1 viral nucleoprotein induced specific immune responses in HHD mice. Vet Res.41(2),24 (2010).
MedlineGoogle Scholar
98 Huang B, Mao CP, Peng S, He L, Hung CF, Wu TC: Intradermal administration of DNA vaccines combining a strategy to bypass antigen processing with a strategy to prolong dendritic cell survival enhances DNA vaccine potency. Vaccine25(45),7824–7831 (2007).
Medline CASGoogle Scholar
99 Hung CF, Calizo R, Tsai YC, He L, Wu TC: A DNA vaccine encoding a single-chain trimer of HLA-A2 linked to human mesothelin peptide generates anti-tumor effects against human mesothelin-expressing tumors. Vaccine25(1),127–135 (2007).
Medline CASGoogle Scholar
100 Kim S, Li L, McMurtrey CP et al.: Single-chain HLA-A2 MHC trimers that incorporate an immundominant peptide elicit protective T cell immunity against lethal West Nile virus infection. J. Immunol.184(8),4423–4430 (2010).
Medline CASGoogle Scholar
101 Pejawar-Gaddy S, Rajawat Y, Hilioti Z et al.: Generation of a tumor vaccine candidate based on conjugation of a MUC1 peptide to polyionic papillomavirus virus-like particles. Cancer Immunol. Immunother.59(11),1685–1696 (2010).
Medline CASGoogle Scholar
102 Gabitzsch ES, Xu Y, Balint JP Jr, Hartman ZC, Lyerly HK, Jones FR: Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA. Cancer Immunol. Immunother.59(7),1131–1135 (2010).
Medline CASGoogle Scholar
103 Kaufman HL, Kim-Schulze S, Manson K et al.: Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer. J. Transl. Med.5,60 (2007).
MedlineGoogle Scholar
104 Morse MA, Hobeika AC, Osada T et al.: An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer. J. Clin. Invest.120(9),3234–3241 (2010).▪ Describes the successful clinical intervention in patients with advanced cancer, including pancreatic cancer, by inducing a protective immune response despite an immunosuppressive environment.
Medline CASGoogle Scholar
105 Ryman KD, Klimstra WB: Host responses to alphavirus infection. Immunol. Rev.225,27–45 (2008).
Medline CASGoogle Scholar
106 Yang L, Yang H, Rideout K et al.: Engineered lentivector targeting of dendritic cells for in vivo immunization. Nat. Biotechnol.26(3),326–334 (2008).
Medline CASGoogle Scholar
107 Bernstein MB, Chakraborty M, Wansley EK et al.: Recombinant Saccharomyces cerevisiae (yeast-CEA) as a potent activator of murine dendritic cells. Vaccine26(4),509–521 (2008).
Medline CASGoogle Scholar
108 Remondo C, Cereda V, Mostbock S et al.: Human dendritic cell maturation and activation by a heat-killed recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen. Vaccine27(7),987–994 (2009).
Medline CASGoogle Scholar
109 Boehm AL, Higgins J, Franzusoff A, Schlom J, Hodge JW: Concurrent vaccination with two distinct vaccine platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations. Cancer Immunol. Immunother.59(3),397–408 (2010).
Medline CASGoogle Scholar
110 Wansley EK, Chakraborty M, Hance KW et al.: Vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicits therapeutic antitumor responses. Clin. Cancer Res.14(13),4316–4325 (2008).
Medline CASGoogle Scholar
111 Lu Y, Bellgrau D, Dwyer-Nield LD et al.: Mutation-selective tumor remission with Ras-targeted, whole yeast-based immunotherapy. Cancer Res.64(15),5084–5088 (2004).
Medline CASGoogle Scholar
112 Paterson Y, Guirnalda PD, Wood LM: Listeria and Salmonella bacterial vectors of tumor-associated antigens for cancer immunotherapy. Semin. Immunol.22(3),183–189 (2010).
Medline CASGoogle Scholar
113 Le DT, Nir-Paz R, Hampl J et al.: Results of Phase I studies testing two live-attenuated listeria vaccines, ANZ-100 and CRS-207, for the treatment of cancer. In: Tumor Immunology: Basic and Clinical Advances. AACR Program and Proceedings. Abstract B12 (2010).
Google Scholar
114 Ishizaki H, Song GY, Srivastava T et al.: Heterologous prime/boost immunization with p53-based vaccines combined with Toll-like receptor stimulation enhances tumor regression. J. Immunother.33(6),609–617 (2010).
Medline CASGoogle Scholar
115 Seavey MM, Maciag PC, Al-Rawi N, Sewell D, Paterson Y: An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2/neu⁺ breast tumors in a mouse model. J. Immunol.182(9),5537–5546 (2009).
Medline CASGoogle Scholar
116 Seavey MM, Pan ZK, Maciag PC et al.: A novel human Her-2/neu chimeric molecule expressed by Listeria monocytogenes can elicit potent HLA-A2 restricted CD8-positive T cell responses and impact the growth and spread of Her-2/neu-positive breast tumors. Clin. Cancer Res.115(3),924–932 (2009).
Google Scholar
117 Shahabi V, Seavey MM, Maciag PC, Rivera S, Wallecha A: Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human. Cancer Gene Ther.18,53–62 (2010).
MedlineGoogle Scholar
118 Niethammer AG, Primus FJ, Xiang R et al.: An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice. Vaccine20(3–4),421–429 (2001).
Medline CASGoogle Scholar
119 Xiang R, Primus FJ, Ruehlmann JM et al.: A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice. J. Immunol.167(8),4560–4565 (2001).
Medline CASGoogle Scholar
120 Xiong G, Husseiny MI, Song L et al.: Novel cancer vaccine based on genes of Salmonella pathogenicity island 2. Int. J. Cancer126(11),2622–2634 (2010).
Medline CASGoogle Scholar
121 Hellstrom I, Friedman E, Verch T et al.: Anti-mesothelin antibodies and circulating mesothelin relate to the clinical state in ovarian cancer patients. Cancer Epidemiol. Biomarkers Prev.17(6),1520–1526 (2008).
Medline CASGoogle Scholar
122 Ho M, Hassan R, Zhang J et al.: Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients. Clin. Cancer Res.11(10),3814–3820 (2005).
Medline CASGoogle Scholar
123 Reichert JM, Valge-Archer VE: Development trends for monoclonal antibody cancer therapeutics. Nat. Rev. Drug Discov.6(5),349–356 (2007).
Medline CASGoogle Scholar
124 Arnould L, Gelly M, Penault-Llorca F et al.: Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br. J. Cancer94(2),259–267 (2006).
Medline CASGoogle Scholar
125 Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV: Fc receptors are required in passive and active immunity to melanoma. Proc. Natl Acad. Sci. USA95(2),652–656 (1998).
Medline CASGoogle Scholar
126 Weiner LM, Surana R, Wang S: Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat. Rev. Immunol.10(5),317–327 (2010).▪ Comprehensive overview on the role of antibodies in immune therapy.
Medline CASGoogle Scholar
127 Hassan R, Bullock S, Premkumar A et al.: Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin. Cancer Res.13(17),5144–5149 (2007).
Medline CASGoogle Scholar
128 Filpula D, Zhao H: Releasable PEGylation of proteins with customized linkers. Adv. Drug Deliv. Rev.60(1),29–49 (2008).
Medline CASGoogle Scholar
129 Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I: Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin. Cancer Res.15(16),5274–5279 (2009).
Medline CASGoogle Scholar
130 Hassan R, Ebel W, Routhier EL et al.: Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin. Cancer Immun.7,20 (2007).
MedlineGoogle Scholar
131 Feng Y, Xiao X, Zhu Z et al.: A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity. Mol. Cancer Ther.8(5),1113–1118 (2009).
Medline CASGoogle Scholar
132 Ho M, Feng M, Fisher RJ, Rader C, Pastan I: A novel high affinity human monoclonal antibody to mesothelin. Int. J. Cancer128(9),2020–2030 (2011).
Medline CASGoogle Scholar
133 Richman PI, Bodmer WF: Monoclonal antibodies to human colorectal epithelium: markers for differentiation and tumour characterization. Int. J. Cancer39(3),317–328 (1987).
Medline CASGoogle Scholar
134 Stewart LM, Young S, Watson G et al.: Humanisation and characterisation of PR1A3, a monoclonal antibody specific for cell-bound carcinoembryonic antigen. Cancer Immunol. Immunother.47(6),299–306 (1999).
Medline CASGoogle Scholar
135 Ashraf SQ, Umana P, Mossner E et al.: Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis. Br. J. Cancer101(10),1758–1768 (2009).
Medline CASGoogle Scholar
136 Conaghan P, Ashraf S, Tytherleigh M et al.: Targeted killing of colorectal cancer cell lines by a humanised IgG₁ monoclonal antibody that binds to membrane-bound carcinoembryonic antigen. Br. J. Cancer98(7),1217–1225 (2008).
Medline CASGoogle Scholar
137 Blumenthal RD, Osorio L, Hayes MK, Horak ID, Hansen HJ, Goldenberg DM: Carcinoembryonic antigen antibody inhibits lung metastasis and augments chemotherapy in a human colonic carcinoma xenograft. Cancer Immunol. Immunother.54(4),315–327 (2005).
Medline CASGoogle Scholar
138 Danielczyk A, Stahn R, Faulstich D et al.: PankoMab: a potent new generation anti-tumour MUC1 antibody. Cancer Immunol. Immunother.55(11),1337–1347 (2006).
Medline CASGoogle Scholar
139 Fan XN, Karsten U, Goletz S, Cao Y: Reactivity of a humanized antibody (hPankoMab) towards a tumor-related MUC1 epitope (TA-MUC1) with various human carcinomas. Pathol. Res. Pract.206(8),585–589 (2010).
Medline CASGoogle Scholar
140 Pratesi G, Petrangolini G, Tortoreto M et al.: Antitumor efficacy of trastuzumab in nude mice orthotopically xenografted with human pancreatic tumor cells expressing low levels of HER-2/neu. J. Immunother.31(6),537–544 (2008).
Medline CASGoogle Scholar
141 Saeki H, Yanoma S, Takemiya S et al.: Antitumor activity of a combination of trastuzumab (Herceptin) and oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2-overexpressing pancreatic cancer. Oncol. Rep.18(2),433–439 (2007).
Medline CASGoogle Scholar
142 Larbouret C, Robert B, Navarro-Teulon I et al.: In vivo therapeutic synergism of anti-epidermal growth factor receptor and anti-HER2 monoclonal antibodies against pancreatic carcinomas. Clin. Cancer Res.13(11),3356–3362 (2007).
Medline CASGoogle Scholar
143 Larbouret C, Robert B, Bascoul-Mollevi C et al.: Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts. Ann. Oncol.21(1),98–103 (2010).
Medline CASGoogle Scholar
144 Hung CF, Tsai YC, He L, Wu TC: Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8⁺ T cells. Gene Ther.14(12),921–929 (2007).
Medline CASGoogle Scholar
145 Kawaoka T, Oka M, Takashima M et al.: Adoptive immunotherapy for pancreatic cancer: cytotoxic T lymphocytes stimulated by the MUC1-expressing human pancreatic cancer cell line YPK-1. Oncol. Rep.20(1),155–163 (2008).
MedlineGoogle Scholar
146 Kondo H, Hazama S, Kawaoka T et al.: Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes. AntiCancer Res.28(1B),379–387 (2008).
Medline CASGoogle Scholar
147 Carpenito C, Milone MC, Hassan R et al.: Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc. Natl Acad. Sci. USA106(9),3360–3365 (2009).
Medline CASGoogle Scholar
148 Davies DM, Maher J: Adoptive T-cell immunotherapy of cancer using chimeric antigen receptor-grafted T cells. Arch. Immunol. Ther. Exp. (Warsz.)58(3),165–178 (2010).
Medline CASGoogle Scholar
149 Emtage PC, Lo AS, Gomes EM, Liu DL, Gonzalo-Daganzo RM, Junghans RP: Second-generation anti-carcinoembryonic antigen designer T cells resist activation-induced cell death, proliferate on tumor contact, secrete cytokines, and exhibit superior antitumor activity in vivo: a preclinical evaluation. Clin. Cancer Res.14(24),8112–8122 (2008).
Medline CASGoogle Scholar
150 Shirasu N, Shibaguci H, Kuroki M, Yamada H, Kuroki M: Construction and molecular characterization of human chimeric T-cell antigen receptors specific for carcinoembryonic antigen. Anti. Cancer Res.30(7),2731–2738 (2010).
Medline CASGoogle Scholar
151 Wilkie S, Burbridge SE, Chiapero-Stanke L et al.: Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J. Biol. Chem.285(33),25538–25544 (2010).
Medline CASGoogle Scholar
152 Bakhtiari SH, Rahbarizadeh F, Hasannia S, Ahmadvand D, Iri-Sofla FJ, Rasaee MJ: Anti-MUC1 nanobody can redirect T-body cytotoxic effector function. Hybridoma (Larchmt)28(2),85–92 (2009).
Medline CASGoogle Scholar
153 Wang H, Wei H, Zhang R et al.: Genetically targeted T cells eradicate established breast cancer in syngeneic mice. Clin. Cancer Res.15(3),943–950 (2009).
Medline CASGoogle Scholar
154 Zhao Y, Wang QJ, Yang S et al.: A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity. J. Immunol.183(9),5563–5574 (2009).
Medline CASGoogle Scholar
155 Koos D, Josephs SF, Alexandrescu DT et al.: Tumor vaccines in 2010: need for integration. Cell Immunol.263(2),138–147 (2010).
Medline CASGoogle Scholar
156 Liyanage UK, Moore TT, Joo HG et al.: Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol.169(5),2756–2761 (2002).
Medline CASGoogle Scholar
157 Tian M, Neil JR, Schiemann WP: Transforming growth factor-β and the hallmarks of cancer. Cell Signal.23(6),951–962 (2011).
Medline CASGoogle Scholar
158 von Bernstorff W, Spanjaard RA, Chan AK et al.: Pancreatic cancer cells can evade immune surveillance via nonfunctional Fas (APO-1/CD95) receptors and aberrant expression of functional Fas ligand. Surgery125(1),73–84 (1999).
Medline CASGoogle Scholar
159 Derre L, Rivals JP, Jandus C et al.: BTLA mediates inhibition of human tumor-specific CD8⁺ T cells that can be partially reversed by vaccination. J. Clin. Invest.120(1),157–167 (2010).
Medline CASGoogle Scholar
160 Witkiewicz A, Williams TK, Cozzitorto J et al.: Expression of indoleamine 2,3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. J. Am. Coll. Surg.206(5),849–854 (2008).
MedlineGoogle Scholar
161 Gabrilovich DI, Nagaraj S: Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol.9(3),162–174 (2009).▪ Comprehensive overview of the suppressor cells population, myeloid-derived supressor cells, and how they can be targeted clinically.
Medline CASGoogle Scholar
162 Almand B, Clark JI, Nikitina E et al.: Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J. Immunol.166(1),678–689 (2001).
Medline CASGoogle Scholar
163 Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ: Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol. Immunother.58(1),49–59 (2009).
Medline CASGoogle Scholar
164 Mishra P, Banerjee D, Ben-Baruch A: Chemokines at the crossroads of tumor-fibroblast interactions that promote malignancy. J. Leukoc. Biol.89(1),31–39 (2011).
Medline CASGoogle Scholar
165 Tan MC, Goedegebuure PS, Belt BA et al.: Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer. J. Immunol. 1 182(3),1746–1755 (2009).
Medline CASGoogle Scholar
166 Munn DH, Mellor AL: Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest.117(5),1147–1154 (2007).
Medline CASGoogle Scholar
167 Katz JB, Muller AJ, Prendergast GC: Indoleamine 2,3-dioxygenase in T-cell tolerance and tumoral immune escape. Immunol. Rev.222,206–221 (2008).
Medline CASGoogle Scholar
168 Weber J: Immune checkpoint proteins: a new therapeutic paradigm for cancer – preclinical background: CTLA-4 and PD-1 blockade. Semin. Oncol.37(5),430–439 (2010).
Medline CASGoogle Scholar
169 Agarwala SS, Ribas A: Current experience with CTLA4-blocking monoclonal antibodies for the treatment of solid tumors. J. Immunother.33(6),557–569 (2010).
Medline CASGoogle Scholar
170 Hodi FS, O’Day SJ, McDermott DF et al.: Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med.363(8),711–723 (2010).
Medline CASGoogle Scholar
171 Royal RE, Levy C, Turner K et al.: Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic Ppancreatic adenocarcinoma. J. Immunother.33(8),828–833 (2010).
Medline CASGoogle Scholar
172 Brahmer JR, Drake CG, Wollner I et al.: Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol.28(19),3167–3175 (2010).
Medline CASGoogle Scholar
173 Berger R, Rotem-Yehudar R, Slama G et al.: Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin. Cancer Res.14(10),3044–3051 (2008).
Medline CASGoogle Scholar
174 Melani C, Sangaletti S, Barazzetta FM, Werb Z, Colombo MP: Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res.67(23),11438–11446 (2007).
Medline CASGoogle Scholar
175 Yang L, DeBusk LM, Fukuda K et al.: Expansion of myeloid immune suppressor Gr⁺CD11b⁺ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell6(4),409–421 (2004).
Medline CASGoogle Scholar
176 Zhang B, Zhang Y, Bowerman NA et al.: Equilibrium between host and cancer caused by effector T cells killing tumor stroma. Cancer Res.68(5),1563–1571 (2008).
Medline CASGoogle Scholar
177 Nishikawa H, Kato T, Tanida K et al.: CD4⁺ CD25⁺ T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc. Natl Acad. Sci. USA100(19),10902–10906 (2003).
Medline CASGoogle Scholar
178 Wang HY, Lee DA, Peng G et al.: Tumor-specific human CD4⁺ regulatory T cells and their ligands: implications for immunotherapy. Immunity20(1),107–118 (2004).
Medline CASGoogle Scholar
179 Ding L, Ellis MJ, Li S et al.: Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature464(7291),999–1005 (2010).▪▪ Describes the successful sequencing of a breast cancer genome, opening up the near-future development of personalized treatments for solid tumors.
Medline CASGoogle Scholar
180 Ley TJ, Mardis ER, Ding L et al.: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature456(7218),66–72 (2008).
Medline CASGoogle Scholar
181 Campbell PJ, Yachida S, Mudie LJ et al.: The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature467(7319),1109–1113 (2010).
Medline CASGoogle Scholar
182 Yachida S, Jones S, Bozic I et al.: Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature467(7319),1114–1117 (2010).
Medline CASGoogle Scholar
183 Segal NH, Parsons DW, Peggs KS et al.: Epitope landscape in breast and colorectal cancer. Cancer Res.68(3),889–892 (2008).
Medline CASGoogle Scholar
184 Sensi M, Anichini A: Unique tumor antigens: evidence for immune control of genome integrity and immunogenic targets for T cell-mediated patient-specific immunotherapy. Clin. Cancer Res.12(17),5023–5032 (2006).
Medline CASGoogle Scholar
185 Huang EH, Kaufman HL: CEA-based vaccines. Expert Rev. Vaccines1(1),49–63 (2002).
Medline CASGoogle Scholar
186 Beatty JD, Romero C, Brown PW, Lawrence W Jr, Terz JJ: Clinical value of carcinoembryonic antigen: diagnosis, prognosis, and follow-up of patients with cancer. Arch. Surg.114(5),563–567 (1979).
Medline CASGoogle Scholar
187 Ona FV, Zamcheck N, Dhar P, Moore T, Kupchik HZ: Carcinoembryonic antigen (CEA) in the diagnosis of pancreatic cancer. Cancer31(2),324–327 (1973).
Medline CASGoogle Scholar
188 Ladjemi MZ, Jacot W, Chardes T, Pelegrin A, Navarro-Teulon I: Anti-HER2 vaccines: new prospects for breast cancer therapy. Cancer Immunol. Immunother.59(9),1295–1312 (2010).
Medline CASGoogle Scholar
189 Lei S, Appert HE, Nakata B, Domenico DR, Kim K, Howard JM: Overexpression of HER2/neu oncogene in pancreatic cancer correlates with shortened survival. Int. J. Pancreatol.17(1),15–21 (1995).
Medline CASGoogle Scholar
190 Yamanaka Y, Friess H, Kobrin MS et al.: Overexpression of HER2/neu oncogene in human pancreatic carcinoma. Hum. Pathol.24(10),1127–1134 (1993).
Medline CASGoogle Scholar
191 Downward J: Targeting RAS and PI3K in lung cancer. Nat. Med.14(12),1315–1316 (2008).
Medline CASGoogle Scholar
192 Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell53(4),549–554 (1988).
Medline CASGoogle Scholar
193 Li M, Bharadwaj U, Zhang R et al.: Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer. Mol. Cancer Ther.7(2),286–296 (2008).
Medline CASGoogle Scholar
194 Hassan R, Laszik ZG, Lerner M, Raffeld M, Postier R, Brackett D: Mesothelin is overexpressed in pancreaticobiliary adenocarcinomas but not in normal pancreas and chronic pancreatitis. Am. J. Clin. Pathol.124(6),838–845 (2005).
Medline CASGoogle Scholar
195 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). Clin. Cancer Res.7(12),3862–3868 (2001).
Medline CASGoogle Scholar
196 Kaneko O, Gong L, Zhang J et al.: A binding domain on mesothelin for CA125/MUC16. J. Biol. Chem.6284(6),3739–3749 (2009).
Google Scholar
197 Tang CK, Katsara M, Apostolopoulos V: Strategies used for MUC1 immunotherapy: human clinical studies. Expert Rev. Vaccines7(7),963–975 (2008).
Medline CASGoogle Scholar
198 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. Br. J. Cancer91(12),2086–2093 (2004).
Medline CASGoogle Scholar
199 Chen F, Wang W, El-Deiry WS: Current strategies to target p53 in cancer. Biochem. Pharmacol.80(5),724–730 (2010).
Medline CASGoogle Scholar
200 Scarpa A, Capelli P, Mukai K et al.: Pancreatic adenocarcinomas frequently show p53 gene mutations. Am. J. Pathol.142(5),1534–1543 (1993).
Medline CASGoogle Scholar
201 Ryan BM, O’Donovan N, Duffy MJ: Survivin: a new target for anti-cancer therapy. Cancer Treat. Rev.35(7),553–562 (2009).
Medline CASGoogle Scholar
202 Kanwar RK, Cheung CH, Chang JY, Kanwar JR: Recent advances in anti-survivin treatments for cancer. Curr. Med. Chem.17(15),1509–1515 (2010).
Medline CASGoogle Scholar
203 Qiao JG, Zhang YQ, Yin YC, Tan Z: Expression of Survivin in pancreatic cancer and its correlation to expression of Bcl-2. World J. Gastroenterol.10(18),2759–2761 (2004).
Medline CASGoogle Scholar
204 Satoh K, Kaneko K, Hirota M, Masamune A, Satoh A, Shimosegawa T: Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors. Cancer92(2),271–278 (2001).
Medline CASGoogle Scholar
205 Liu JP, Chen W, Schwarer AP, Li H: Telomerase in cancer immunotherapy. Biochim. Biophys. Acta1805(1),35–42 (2010).
Medline CASGoogle Scholar
206 Hiyama E, Kodama T, Shinbara K et al.: Telomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res.57(2),326–331 (1997).
Medline CASGoogle Scholar
207 Shibuya M: Vascular endothelial growth factor (VEGF)-receptor2: its biological functions, major signaling pathway, and specific ligand VEGF-E. Endothelium13(2),63–69 (2006).
Medline CASGoogle Scholar
208 Itakura J, Ishiwata T, Friess H et al.: Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin. Cancer Res.3(8),1309–1316 (1997).
Medline CASGoogle Scholar
301 The International Clinical Trials Registry offers a registration of all interventional clinical trials conforming to WHO standards International Clinical Trials registry ID number: JPRN-UMIN000001664 http://apps.who.int/trialsearch/trial.aspx?trialid=JPRN-UMIN000001664
Google Scholar
302 Amplimmune Inc. is a company that is involved in developing immune-based biologics to treat patients in the fields of cancer, autoimmunity, transplantation and infectious disease www.amplimmune.com
Google Scholar

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Published online 4 April 2011

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Financial & competing interests disclosure

Lindzy F Dodson is funded through a postdoctoral fellowship from the American Cancer Society, and this work was partially funded by NIH 1R21CA150945-01 to William G Hawkins. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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Potential targets for pancreatic cancer immunotherapeutics

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