Epitopes described in "In vitro stimulation with WT1 peptide-loaded Epstein-Barr virus-positive B cells elicits high frequencies of WT1 peptide-specific T cells with in vitro and in vivo tumoricidal activity."

Reference
Article Authors:Ekaterina S Doubrovina; Mikhail M Doubrovin; Sangyull Lee; Jae-Hung Shieh; Glen Heller; Eric Pamer; Richard J O'Reilly
Article Title:In vitro stimulation with WT1 peptide-loaded Epstein-Barr virus-positive B cells elicits high frequencies of WT1 peptide-specific T cells with in vitro and in vivo tumoricidal activity.
Reference Detail
Reference ID:1005915
Abstract:The Wilms tumor protein (WT1) is overexpressed in most acute and chronic leukemias. To develop a practicable, clinically applicable approach for generation of WT1-specific T cells and to comparatively evaluate the immunogenicity of WT1 in normal individuals, we sensitized T cells from 13 HLA-A0201+ and 5 HLA-A2402+ donors with autologous EBV-transformed B cells or cytokine-activated monocytes, loaded with the HLA-A0201-binding WT1 peptides (126-134)RMFPNAPYL or (187-195)SLGEQQYSV or a newly identified HLA-A2402-binding WT1 peptide (301-310)RVPGVAPTL. WT1-specific T cells were regularly generated from each donor. T cells sensitized with peptide-loaded EBV-transformed B cells generated higher numbers of WT1-specific T cells than peptide-loaded cytokine-activated monocytes. Contrary to expectations, the frequencies of WT1 peptide-specific T cells were equivalent to those generated against individual highly immunogenic HLA-A0201-binding EBV peptides. Each of these T-cell lines specifically killed WT1+ leukemias and solid tumors in an HLA-restricted manner but did not lyse autologous or HLA-matched normal CD34+ hematopoietic progenitor cells or reduce their yield of colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), or mixed colonies (CFU-mix). Furthermore, WT1 peptide-specific T cells after adoptive transfer into nonobese diabetic-severe combined immunodeficient mice bearing subcutaneous xenografts of WT1+ and WT1- HLA-A0201+ leukemias preferentially accumulated in and induced regressions of WT1+ leukemias that expressed the restricting HLA allele. Such cells are clinically applicable and may prove useful for adoptive cell therapy of WT1+ malignant diseases in humans.
Affiliations:Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Date:2004
Reference Type:Literature
PubMed ID:15534094
Journal:Clin Cancer Res
Journal Volume:10
Article Pages:7207-19
Journal ISSN:1078-0432
Article Chemical List:Antigens, CD34;Cytokines;Peptides;WT1 Proteins
Article MeSH List:Alleles; Animals; Antigens, CD34(biosynthesis); Cell Line, Tumor; Cell Movement; Cytokines(metabolism); Genes, Wilms Tumor; Herpesvirus 4, Human(genetics); Humans; Image Processing, Computer-Assisted; Mice; Mice, SCID; Monocytes(metabolism); Neoplasm Transplantation; Peptides(chemistry); Protein Binding; Sensitivity and Specificity; T-Lymphocytes(immunology; metabolism); Time Factors; WT1 Proteins(chemistry; pharmacology)
Curation Last Updated:2012-09-25 20:14:01