Identification of a novel murine pancreatic tumour antigen, which elicits antibody responses in patients with pancreatic carcinoma.
Pancreatic cancer is the fourth leading cause of cancer related death in the United States. Despite numerous efforts in developing new therapies, the prognosis for patients with pancreatic cancer remains poor. Mouse models for spontaneous pancreatic cancer represent an ideal system to develop immunotherapeutic approaches. The aim of this study was to identify new tumour antigens in a murine model that mimics human disease closely, and to verify the results in patients with pancreatic cancer. We analysed a murine pancreatic complementary DNA expression library with serum from tumour-bearing mice, which led to the identification and isolation of several antigens. One of the antigens repeatedly identified in this screening was Tankyrase-2. Here, we show Tankyrase-2 as an antigen eliciting humoral responses not only in mice with established tumours, but also in mice with pre-malignant lesions. Finally, antibody responses to Tankyrase-2 were found in the serum of patients with pancreatic cancer. Reverse transcriptase-polymerase chain reaction analysis showed Tankyrase-2 expression in human pancreatic tumour. These findings show the relevance of spontaneous murine tumour models for the identification of human tumour antigens.
Zhao
Fei
F
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
Vermeer
Benjamin
B
Lehmann
Ulrich
U
Kreipe
Hans
H
Manns
Michael P
MP
Korangy
Firouzeh
F
Greten
Tim F
TF
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015723:Gene Library; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000276:immunology*; D011230:Precancerous Conditions / Q000276:immunology; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D038501:Tankyrases / Q000276:immunology / Q000378:metabolism
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D012334:RNA, Neoplasm; D038501:Tankyrases; C511054:tankyrase-2, mouse
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4760-5
10781081
Curr Opin Immunol. 1997 Oct;9(5):709-16
9368781
Mol Cell Biol. 2006 Mar;26(6):2037-43
16507984
J Clin Oncol. 2008 Jul 20;26(21):3478-80
18640927
J Exp Med. 2004 Aug 2;200(3):297-306
15289501
Lancet. 2004 Mar 27;363(9414):1049-57
15051286
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6919-23
9618514
J Biol Chem. 2001 Sep 21;276(38):35891-9
11454873
Immunol Rev. 2002 Oct;188:22-32
12445278
Clin Cancer Res. 2001 Jan;7(1):113-9
11205898
Int J Cancer. 2008 Nov 15;123(10):2239-46
18712725
J Biol Chem. 2000 Dec 8;275(49):38437-44
10988299
Biochem Biophys Res Commun. 2001 Mar 9;281(4):936-44
11237751
Int J Cancer. 2006 Jul 1;119(1):117-25
16432832
Cancer Res. 2006 Jan 1;66(1):508-16
16397267
Nat Rev Cancer. 2005 Jun;5(6):459-67
15905855
Br J Cancer. 2006 Feb 13;94(3):341-5
16421589
Gastroenterology. 1998 Nov;115(5):1254-62
9797382
Mol Cell Biol. 2002 Jan;22(1):332-42
11739745
Genes Immun. 2001 Feb;2(1):52-5
11294570
Gastroenterology. 2002 Dec;123(6):2052-63
12454861
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12198-203
11027314
Clin Cancer Res. 2004 Jul 1;10(13):4332-41
15240519
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
18287387
Curr Opin Immunol. 2004 Apr;16(2):143-50
15023405
J Exp Med. 2000 Feb 21;191(4):625-30
10684854
Genes Dev. 2001 Feb 1;15(3):286-93
11159909
Immunol Rev. 2008 Apr;222:162-79
18364001