Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination
<p>Abstract</p> <p>Background</p> <p>Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-01-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/8/1/5 |
| _version_ | 1818806299899461632 |
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| author | Ochsenreither Sebastian Nonnenmacher Anika Scheibenbogen Carmen Letsch Anne Busse Antonia Thiel Eckhard Keilholz Ulrich |
| author_facet | Ochsenreither Sebastian Nonnenmacher Anika Scheibenbogen Carmen Letsch Anne Busse Antonia Thiel Eckhard Keilholz Ulrich |
| author_sort | Ochsenreither Sebastian |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation.</p> <p>Methods</p> <p>All patients had been enrolled in a WT1 peptide phase II vaccination trial (NCT00153582) and ultimately progressed despite induction of a WT1 specific T cell response. Blood and bone marrow samples prior to vaccination and during progression were analyzed for mRNA expression level of WT1. Base exchanges within the epitope sequence or flanking regions (10 amino acids N- and C-terminal of the epitope) were assessed with melting point analysis and sequencing. HLA class I expression and WT1 protein expression was analyzed by flow cytometry.</p> <p>Results</p> <p>Only in one patient, downregulation of WT1 mRNA by 1 log and loss of WT1 detection on protein level at time of disease progression was observed. No mutation leading to a base exchange within the epitope sequence or epitope flanking sequences could be detected in any patient. Further, no loss of HLA class I expression on leukemic blasts was observed.</p> <p>Conclusion</p> <p>Defects in antigen presentation caused by loss or mutation of WT1 or downregulation of HLA molecules are not the major basis for escape from the immune response induced by WT1 peptide vaccination.</p> |
| first_indexed | 2024-12-18T19:07:34Z |
| format | Article |
| id | doaj.art-fe2da17fdaff4bc080652e4ba6ee0589 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-18T19:07:34Z |
| publishDate | 2010-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-fe2da17fdaff4bc080652e4ba6ee05892022-12-21T20:56:23ZengBMCJournal of Translational Medicine1479-58762010-01-0181510.1186/1479-5876-8-5Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccinationOchsenreither SebastianNonnenmacher AnikaScheibenbogen CarmenLetsch AnneBusse AntoniaThiel EckhardKeilholz Ulrich<p>Abstract</p> <p>Background</p> <p>Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation.</p> <p>Methods</p> <p>All patients had been enrolled in a WT1 peptide phase II vaccination trial (NCT00153582) and ultimately progressed despite induction of a WT1 specific T cell response. Blood and bone marrow samples prior to vaccination and during progression were analyzed for mRNA expression level of WT1. Base exchanges within the epitope sequence or flanking regions (10 amino acids N- and C-terminal of the epitope) were assessed with melting point analysis and sequencing. HLA class I expression and WT1 protein expression was analyzed by flow cytometry.</p> <p>Results</p> <p>Only in one patient, downregulation of WT1 mRNA by 1 log and loss of WT1 detection on protein level at time of disease progression was observed. No mutation leading to a base exchange within the epitope sequence or epitope flanking sequences could be detected in any patient. Further, no loss of HLA class I expression on leukemic blasts was observed.</p> <p>Conclusion</p> <p>Defects in antigen presentation caused by loss or mutation of WT1 or downregulation of HLA molecules are not the major basis for escape from the immune response induced by WT1 peptide vaccination.</p>http://www.translational-medicine.com/content/8/1/5 |
| spellingShingle | Ochsenreither Sebastian Nonnenmacher Anika Scheibenbogen Carmen Letsch Anne Busse Antonia Thiel Eckhard Keilholz Ulrich Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination Journal of Translational Medicine |
| title | Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination |
| title_full | Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination |
| title_fullStr | Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination |
| title_full_unstemmed | Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination |
| title_short | Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination |
| title_sort | mutation or loss of wilms tumor gene 1 wt1 are not major reasons for immune escape in patients with aml receiving wt1 peptide vaccination |
| url | http://www.translational-medicine.com/content/8/1/5 |
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