Document Detail


Potential target antigens for immunotherapy in human pancreatic cancer.
MedLine Citation:
PMID:  17320278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin. METHODS: Pancreatic adenocarcinoma tumor samples (n=130) were obtained intraoperatively, control tissues (n=23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues. RESULTS: Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2. CONCLUSIONS: Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy.
Authors:
F H Schmitz-Winnenthal; L V Galindo-Escobedo; D Rimoldi; W Geng; P Romero; M Koch; J Weitz; R Krempien; A G Niethammer; P Beckhove; M W Buchler; K Z'graggen
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Publication Detail:
Type:  Journal Article     Date:  2007-02-22
Journal Detail:
Title:  Cancer letters     Volume:  252     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-05-30     Completed Date:  2007-10-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  290-8     Citation Subset:  IM    
Affiliation:
Department of General Surgery, University Hospital of Heidelberg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / immunology,  therapy*
Antigens, Neoplasm / immunology*
Azacitidine / administration & dosage
Base Sequence
DNA Primers
Humans
Immunotherapy*
Pancreatic Neoplasms / immunology,  therapy*
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/DNA Primers; 320-67-2/Azacitidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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