Mutation or loss of Wilms’ tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination | Busse et al. Journal of Translational Medicine 2010 8 5 http content 8 1 5 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Mutation or loss of Wilms tumor gene 1 WT1 are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination Antonia Busse 1 Anne Letsch1 Carmen Scheibenbogen2 Anika Nonnenmacher1 Sebastian Ochsenreither1 Eckhard Thiel1 Ulrich Keilholz1 Abstract Background 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. Methods 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. Results 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. Conclusion 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. Background Over-expression of Wilms tumor gene 1 WT1 is present in a variety of malignant tumors including
