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

• Published in: Nagoya journal of medical science Vol. 85; no. 4; pp. 779 - 796
• Main Authors: Katsuyama, Naoya, Kawase, Takakazu, Barakat, Carolyne, Mizuno, Shohei, Tomita, Akihiro, Ozeki, Kazutaka, Nishio, Nobuhiro, Sato, Yoshie, Kajiya, Ryoko, Shiraishi, Keiko, Takahashi, Yoshiyuki, Ichinohe, Tatsuo, Nishikawa, Hiroyoshi, Akatsuka, Yoshiki
• Format: Journal Article
• Language: English
• Published: Japan Nagoya University 01.11.2023
• Subjects: Chronic Disease; Hematopoietic Stem Cell Transplantation; HLA-DP beta-Chains - genetics; Humans; Leukemia - therapy; Original Paper; Peptides; Receptors, Antigen, T-Cell - genetics; Recurrence; T-Lymphocytes; Transplantation, Homologous; leukemia; GVHD; allogeneic transplantation; TCR-T
• ISSN: 0027-7622; 2186-3326
• DOI: 10.18999/nagjms.85.4.779

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.