1999 Fiscal Year Final Research Report Summary
Analysis of T-cell clone indicating GVL effect due to allo stem cell transplantation and donor lymphocytes infusion.
| Project/Area Number |
10670975
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Fukuoka University |
|---|
Principal Investigator |
KIMURA Nobuhiro Fukuoka Univ., Sch. of Medicine, Assoc. Prof., 医学部, 講師 (40136445)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAMURA Kazuo Fukuoka Univ., Sch. of Medicine, Professor, 医学部, 教授 (60145422)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | Vβ repertoire / Donor lymphocytes infusion / Allo-BMT / T-cell receptor / Graft versus leukemia |
|---|
| Research Abstract |
Several reports have demonstrated the persistent detection of AML1/MTG8 fusion products, representing minimal residual disease (MRD), in patients with t(8 ; 21) acute myelogenous leukemia (AML) who are in long-term remission. It is probable that immune-mediated mechanisms that are able to suppress the expansion of MRD may result in the continuance of remission. It was previously shown that some t(8 ; 21) AML patients had high anti-MTG8 antibody titers. MTG8 expression in normal adult tissue is either not detectable or else only faintly detectable. We made the hypothesis that the orverexpression of the MTG8 gene in t(8 ; 21) AML cells could act as a possible tumor antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b aa182-191) using monocyte-derived dendritic cells from a healthy donor. T cell receptor (TCR) Vα17, TCRVβ14 and 15 and TCR
… More
Jβ2.1 and predominantly used in these CTL lines. Our data which suggest that the MTG8 protein could be one of the tumor antigens recognized by CTLs may be helpful in further investigations of TCR analysis in t(8 ; 21) AML patients with HLA-A0201 who are in long-term remission.
Hematologic relapse of chronic myeloid leukemia (CML) developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte infusion (DLI) twice at a dose of 5x10ィイD16ィエD1/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLI, and has remained in a CCR state for 17 months. Neither acute chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the TCR repertoire disclosed oligoclonal of T cells of the TCR Vβ and Jβ subfamilies. These observed provide evidence for the clonal expansion of allogeneic T cells that are capable of mediation antileukemic activity without causing GVHD. Less
|
