| RRC ID |
77871
|
| Author |
Katsuyama N, Kawase T, Barakat C, Mizuno S, Tomita A, Ozeki K, Nishio N, Sato Y, Kajiya R, Shiraishi K, Takahashi Y, Ichinohe T, Nishikawa H, Akatsuka Y.
|
| Title |
T cell receptor-engineered T cells derived from target human leukocyte antigen-DPB1-specific T cell can be a potential tool for therapy against leukemia relapse following allogeneic hematopoietic cell transplantation.
|
| Journal |
Nagoya J Med Sci
|
| Abstract |
Human leukocyte antigen (HLA)-DPB1 antigens are mismatched in approximately 70% of allogeneic hematopoietic stem cell transplantations (allo-HSCT) from HLA 10/10 matched unrelated donors. HLA-DP-mismatched transplantation was shown to be associated with an increase in acute graft-versus-host disease (GVHD) and a decreased risk of leukemia relapse due to the graft-versus-leukemia (GVL) effect. Immunotherapy targeting mismatched HLA-DP is considered reasonable to treat leukemia following allo-HCT if performed under non-inflammatory conditions. Therefore, we isolated CD4+ T cell clones that recognize mismatched HLA-DPB1 from healthy volunteer donors and generated T cell receptor (TCR)-gene-modified T cells for future clinical applications. Detailed analysis of TCR-T cells expressing TCR from candidate clone #17 demonstrated specificity to myeloid and monocytic leukemia cell lines that even expressed low levels of targeted HLA-DP. However, they did not react to non-hematopoietic cell lines with a substantial level of targeted HLA-DP expression, suggesting that the TCR recognized antigenic peptide is only present in some hematopoietic cells. This study demonstrated that induction of T cells specific for HLA-DP, consisting of hematopoietic cell lineage-derived peptide and redirection of T cells with cloned TCR cDNA by gene transfer, is feasible when using careful specificity analysis.
|
| Volume |
85(4)
|
| Pages |
779-796
|
| Published |
2023-11-1
|
| DOI |
10.18999/nagjms.85.4.779
|
| PMID |
38155626
|
| PMC |
PMC10751490
|
| MeSH |
Chronic Disease
HLA-DP beta-Chains / genetics
Hematopoietic Stem Cell Transplantation*
Humans
Leukemia* / therapy
Peptides
Receptors, Antigen, T-Cell / genetics
Recurrence
T-Lymphocytes
Transplantation, Homologous
|
| IF |
0.762
|
| Resource |
| Human and Animal Cells |
HYT-1(RCB1297)
THP-1(RCB3686) |
