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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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. 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 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.

Original languageEnglish
Pages (from-to)779-796
Number of pages18
JournalNagoya journal of medical science
Volume85
Issue number4
DOIs
Publication statusPublished - 2023

All Science Journal Classification (ASJC) codes

  • General Medicine

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