Identification of a novel WT1‐derived peptide which induces human leucocyte antigen‐A24‐restricted anti‐leukaemia cytotoxic T lymphocytes

Abstract

Summary. We previously reported the establishment of a Wilms' tumour (WT)1-derived peptide (CMTWNQMNL)-specific and human leucocyte antigen (HLA)-A24-restricted anti-leukaemia cytotoxic T lymphocyte (CTL) line, TAK-1. In this study, we have established a novel WT1-derived peptide (RWPSCQKKF)-specific CD8 + CTL line, designated NIM-1. NIM-1 lysed HLA-A24-positive leukaemia cells, but not HLA-A24-negative leukaemia cells or normal cells. The effects of TAK-1 and NIM-1 on cytotoxicity against leukaemia cells were not synergistic, suggesting that recognition of a single epitope on the tumour-specific antigen by CTLs is sufficient to exert maximal cytotoxic activity against tumour cells.

Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities

“…24 WT1, a pro-oncogenic protein overexpressed in hematologic and oncologic malignancies, 16 is being evaluated as a target protein for immunotherapy. 17 As only few epitopes are defined so far, [25][26][27] we examined if novel WT1-specific epitopes could be identified by selecting for CD137 ϩ T cells responding to stimulation with a peptide library, consisting of 15-mers spanning the complete WT1 protein with each overlapping by 11 amino acids. Naive CD8 ϩ T cells from healthy donors were stimulated with autologous DCs pulsed with the peptide library and restimulated twice.…”

Prophylactic transfer of BCR-ABL–, PR1-, and WT1-reactive donor T cells after T cell–depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia

“…Human leukocyte Ag-restricted peptides derived from proteinase 3 (human leukocyte Ag-A2, VLQELNVTV 23 ), WT1 (human leukocyte Ag-A2, RMFPNAPYL 24 ; human leukocyte Ag-A24, RWPSCQKKF 25 ), and B-cell receptor-ABL (human leukocyte Ag-A3, KQSSKALQR; human leukocyte Ag-A3/human leukocyte Ag-A11, HSATGFKQSSK; human BCR-ABL-, PR1-, AND WT1-REACTIVE DONOR T CELLS 7175 BLOOD, 30 JUNE 2011 ⅐ VOLUME 117, NUMBER 26 For personal use only. on April 7, 2019.…”

Myeloma Cells Are Highly Sensitive to the Granule Exocytosis Pathway Mediated by WT1-Specific Cytotoxic T Lymphocytes

“…A CTL clone designated TAK-1, which specifically recognizes WT1-T2 peptide in the context of HLA-A*2402, was established as described previously (16,21). Briefly, CD8 ϩ T lymphocytes were stimulated repeatedly with WT1-T2 peptide-loaded dendritic cells.…”