Wilms' Tumour 1 (WT1) peptide vaccination in patients with acute myeloid leukaemia induces short‐lived WT1‐specific immune responses. (16th November 2013)

• Record Type: Journal Article
• Authors: Uttenthal, Benjamin; Martinez‐Davila, Irma; Ivey, Adam; Craddock, Charles; Chen, Frederick; Virchis, Andras; Kottaridis, Panagiotis; Grimwade, David; Khwaja, Asim; Stauss, Hans; Morris, Emma C.
• Is Part Of: British journal of haematology. Volume 164:Number 3(2014:Feb.)
• Page Start: 366
• Page End: 375
• Publication Date: 2013-11-16
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12637
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12637-abs-0001"> <title>Summary</title> <p>Wilms' Tumour 1 (WT1) is a zinc finger transcription factor that is over‐expressed in acute myeloid leukaemia (AML). Its restricted expression in normal tissues makes it a promising target for novel immunotherapies aiming to accentuate the cytotoxic T lymphocyte (CTL) response against AML. Here we report a phase I/II clinical trial of subcutaneous peptide vaccination with two separate HLA‐A2‐binding peptide epitopes derived from WT1, together with a pan‐DR binding peptide epitope (PADRE), in Montanide adjuvant. Eight HLA‐A2‐positive patients with poor risk AML received five vaccination cycles at 3‐weekly intervals. The three cohorts received 0·3, 0·6 and 1 mg of each peptide, respectively. In six patients, WT1‐specific CTL responses were detected using enzyme‐linked immunosorbent spot assays and pWT126/HLA‐A*0201 tetramer staining, after <italic>ex vivo</italic> stimulation with the relevant WT1 peptides. However, re‐stimulation of these WT1‐specific T cells failed to elicit secondary expansion in all four patients tested, suggesting that the WT1‐specific CD8⁺ T cells generated following vaccination may be functionally impaired. No correlation was observed between peptide dose, cellular immune response, reduction in <italic>WT1 </italic>mRNA expression and clinical response. Larger studies are indicated to confirm these findings.</p> </abstract>