| Autor: |
Naoya Katsuyama, Takakazu Kawase, Carolyne Barakat, Shohei Mizuno, Akihiro Tomita, Kazutaka Ozeki, Nobuhiro Nishio, Yoshie Sato, Ryoko Kajiya, Keiko Shiraishi, Yoshiyuki Takahashi, Tatsuo Ichinohe, Hiroyoshi Nishikawa, Yoshiki Akatsuka |
| Předmět: |
|
| Zdroj: |
Nagoya Journal of Medical Science; Nov2023, Vol. 85 Issue 4, p779-796, 18p |
| Abstrakt: |
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. HLADP-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 alloHCT 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
