Home LiteratureArticle Details
PMID: 23323149 Published · ppublish English Journal Article

Immunotherapy updates in pancreatic cancer: are we there yet?

Therapeutic advances in medical oncology ·Vol. 5 ·No. 1 ·2013-01-00 ·Pages 81-9

Gunturu KS, Rossi GR, Saif MW

Abstract

Pancreatic cancer is a lethal disease and remains one of the most resistant cancers to traditional therapies. Historically, chemotherapy or radiotherapy did not provide meaningful survival benefit in advanced pancreatic cancer. Gemcitabine and recently FOLFIRINOX (5-flourouracil, leucovorin, oxaliplatin and irinotecan) have provided some limited survival advantage in advanced pancreatic cancer. Targeted agents in combination with gemcitabine had not shown significant improvement in the survival. Current therapies for pancreatic cancer have their limitations; thus, we are in dire need of newer treatment options. Immunotherapy in pancreatic cancer works by recruiting and activating T cells that recognize tumor-specific antigens which is a different mechanism compared with chemotherapy and radiotherapy. Preclinical models have shown that immunotherapy and targeted therapies like vascular endothelial growth factor and epidermal growth factor inhibitors work synergistically. Hence, new immunotherapy and targeted therapies represent a viable option for pancreatic cancer. In this article, we review the vaccine therapy for pancreatic cancer.

Keywords
immunotherapy pancreatic cancer vaccine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gunturu Krishna Soujanya
Division of Hematology/Onocology and Department of Medicine and Cancer Center, Tufts Medical Center, Boston, MA, USA.
Rossi Gabriela R
Saif Muhammad Wasif
References (46)
46 references, click to expand
  1. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells.
    J Biol Chem. 1988 Nov 25;263(33):17755-62 PMID: 2460463
  2. Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I/II clinical trial.
    Cancer Immunol Immunother. 2002 Dec;51(11-12):669-73 PMID: 12439613
  3. 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. 2001 Jan 1;19(1):145-56 PMID: 11134207
  4. 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. 2005 Mar;54(3):254-64 PMID: 15372205
  5. Global cancer statistics.
    CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90 PMID: 21296855
  6. Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations.
    Cell Immunol. 1997 Dec 15;182(2):137-51 PMID: 9514698
  7. Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients.
    Cancer Res. 1994 Jun 1;54(11):2856-60 PMID: 7514493
  8. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.
    Cell. 1988 May 20;53(4):549-54 PMID: 2453289
  9. Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model.
    Cancer Immunol Immunother. 2011 Jan;60(1):99-109 PMID: 20960189
  10. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial.
    JAMA. 2008 Mar 5;299(9):1019-26 PMID: 18319412
  11. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.
    JAMA. 2007 Jan 17;297(3):267-77 PMID: 17227978
  12. Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas.
    Ann Surg. 2004 Aug;240(2):293-8 PMID: 15273554
  13. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539-43 PMID: 8097319
  14. Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer.
    J Transl Med. 2007 Nov 26;5:60 PMID: 18039393
  15. Heat shock protein-based cancer vaccines.
    Expert Rev Vaccines. 2004 Aug;3(4):403-11 PMID: 15270645
  16. TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family.
    Cell. 1997 Mar 21;88(6):875-84 PMID: 9118230
  17. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.
    N Engl J Med. 2011 May 12;364(19):1817-25 PMID: 21561347
  18. Survivin DNA vaccine generated specific antitumor effects in pancreatic carcinoma and lymphoma mouse models.
    Vaccine. 2007 Nov 14;25(46):7955-61 PMID: 17933439
  19. Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine.
    Am J Clin Oncol. 2011 Jun;34(3):321-5 PMID: 20686403
  20. Immunotherapy for pancreatic cancer - science driving clinical progress.
    Nat Rev Cancer. 2005 Jun;5(6):459-67 PMID: 15905855
  21. A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma.
    Cancer Chemother Pharmacol. 2012 Feb;69(2):415-24 PMID: 21800112
  22. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study.
    Br J Cancer. 2006 Dec 4;95(11):1474-82 PMID: 17060934
  23. Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database.
    Cancer. 2007 Aug 15;110(4):738-44 PMID: 17580363
  24. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation.
    Ann Surg. 2011 Feb;253(2):328-35 PMID: 21217520
  25. The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer.
    Int J Gastrointest Cancer. 2002;32(1):1-6 PMID: 12630764
  26. 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. 2006 Oct;55(10):1294-8 PMID: 16315030
  27. Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome.
    J Clin Oncol. 2005 Aug 1;23(22):5099-107 PMID: 15983396
  28. Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in patients with advanced pancreatic carcinoma.
    Pancreas. 2012 Mar;41(2):195-205 PMID: 21792083
  29. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma.
    Int J Cancer. 2001 May 1;92(3):441-50 PMID: 11291084
  30. A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer.
    Clin Exp Med. 2012 Sep;12(3):173-80 PMID: 21932124
  31. Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors.
    Cancer. 2001 Jul 15;92(2):271-8 PMID: 11466679
  32. Cancer statistics, 2010.
    CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300 PMID: 20610543
  33. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas.
    J Clin Oncol. 2005 Feb 1;23(4):720-31 PMID: 15613691
  34. Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study.
    Int J Cancer. 1996 Feb 8;65(4):450-3 PMID: 8621226
  35. Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation.
    Lancet. 1995 Nov 25;346(8987):1399-400 PMID: 7475823
  36. Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer.
    Am J Gastroenterol. 1998 Oct;93(10):1967-71 PMID: 9772067
  37. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma.
    J Immunother. 2010 Oct;33(8):828-33 PMID: 20842054
  38. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase.
    Oncogene. 1998 Mar 5;16(9):1217-22 PMID: 9528864
  39. A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma.
    Dig Dis Sci. 2007 Aug;52(8):1964-72 PMID: 17420942
  40. Complete protection against melanoma in absence of autoimmune depigmentation after rejection of melanoma cells expressing alpha(1,3)galactosyl epitopes.
    Cancer Immunol Immunother. 2005 Oct;54(10):999-1009 PMID: 15889257
  41. Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1----3Gal epitope in primates.
    Proc Natl Acad Sci U S A. 1987 Mar;84(5):1369-73 PMID: 2434954
  42. Telomerase activity in human solid tumors. Diagnostic utility and clinical applications.
    Am J Clin Pathol. 1999 Jul;112(1 Suppl 1):S68-75 PMID: 10396302
  43. Allogeneic melanoma vaccine expressing alphaGal epitopes induces antitumor immunity to autologous antigens in mice without signs of toxicity.
    J Immunother. 2008 Jul-Aug;31(6):545-54 PMID: 18528300
  44. The RNA component of human telomerase.
    Science. 1995 Sep 1;269(5228):1236-41 PMID: 7544491
  45. Telomerase catalytic subunit homologs from fission yeast and human.
    Science. 1997 Aug 15;277(5328):955-9 PMID: 9252327
  46. Effective treatment of preexisting melanoma with whole cell vaccines expressing alpha(1,3)-galactosyl epitopes.
    Cancer Res. 2005 Nov 15;65(22):10555-61 PMID: 16288048
Article Info
Journal
Therapeutic advances in medical oncology
Abbr.
Ther Adv Med Oncol
ISSN
1758-8340
DOI
10.1177/1758834012462463
Published
2013-01-00
Pages
81-9
Language
English
Region
England
NLM ID
101510808
PMCID
PMC3539275
External Links
PubMed source DOI: 10.1177/1758834012462463 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2