Abstract
Feasibility of gene-immunotherapy using WT1-specific T-cell receptor gene transfer for infant acute lymphoblastic leukemia with MLL gene rearrangement
Highlights
Infant acute lymphoblastic leukemia (ALL) with rearrangement of the mixed-lineage leukemia (MLL) gene shows a poor outcome, despite intensive chemotherapy followed by hematopoietic stem cell transplantation at first remission.[1]
The cytotoxicity mediated by WT1-T-cell receptor (TCR) cytotoxic T lymphocyte (CTL) against ALL cell lines with MLL rearrangement was significantly inhibited by addition of anti-HLA class I framework monoclonal antibody but not by anti-HLA-DR monoclonal antibody. These results show that WT1-TCR CTLs can exert cytotoxicity against ALL cell lines with MLL rearrangement in an HLA-A*24:02-restricted manner through recognition of the WT1235À243 epitope that is naturally processed from WT1 protein in ALL cells and presented on the cell surface in the context of HLA class I molecules
We examined whether WT1-TCR CTLs can lyse infant ALL cells with MLL rearrangement freshly isolated from the patients
Summary
Infant acute lymphoblastic leukemia (ALL) with rearrangement of the mixed-lineage leukemia (MLL) gene shows a poor outcome, despite intensive chemotherapy followed by hematopoietic stem cell transplantation at first remission.[1]. We verified the feasibility of adoptive immunotherapy for MLL gene-rearranged infant ALL using T lymphocytes genetically engineered by WT1-specific T-cell receptor (TCR) gene transfer. Expression of WT1 mRNA appeared to be significantly higher in leukemia cells of ALL infants with MLL gene rearrangement (n 1⁄4 41) than in those of ALL patients with germline configuration (n 1⁄4 19) (t-test; Po0.01).
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