PMID- 37310580
OWN - NLM
STAT- MEDLINE
DCOM- 20230721
LR  - 20230721
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 118
IP  - 2
DP  - 2023 Aug
TI  - Development of TCR-T cell therapy targeting mismatched HLA-DPB1 for relapsed 
      leukemia after allogeneic transplantation.
PG  - 252-266
LID - 10.1007/s12185-023-03621-y [doi]
AB  - Relapsed leukemia after allogeneic hematopoietic stem cell transplantation 
      (allo-HSCT) remains a significant challenge, with the re-emergence of the primary 
      disease being the most frequent cause of death. Human leukocyte antigen 
      (HLA)-DPB1 mismatch occurs in approximately 70% of unrelated allo-HSCT cases, and 
      targeting mismatched HLA-DPB1 is considered reasonable for treating relapsed 
      leukemia following allo-HSCT if performed under proper conditions. In this study, 
      we established several clones restricted to HLA-DPB1*02:01, -DPB1*04:02, and 
      -DPB1*09:01 from three patients who underwent HLA-DPB1 mismatched allo-HSCT using 
      donor-derived alloreactive T cells primed to mismatched HLA-DPB1 in the 
      recipient's body after transplantation. A detailed analysis of the 
      DPB1*09:01-restricted clone 2A9 showed reactivity against various leukemia cell 
      lines and primary myeloid leukemia blasts, even with low HLA-DP expression. T 
      cell receptor (TCR)-T cells derived from clone 2A9 retained the ability to 
      trigger HLA-DPB1*09:01-restricted recognition and lysis of various leukemia cell 
      lines in vitro. Our study demonstrated that the induction of mismatched HLA-DPB1 
      specific T cell clones from physiologically primed post-allo-HSCT alloreactive 
      CD4(+) T cells and the redirection of T cells with cloned TCR cDNA by gene 
      transfer are feasible as techniques for future adoptive immunotherapy.
CI  - (c) 2023. Japanese Society of Hematology.
FAU - Barakat, Carolyne
AU  - Barakat C
AD  - Department of Immunology, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
FAU - Inagaki, Yuichiro
AU  - Inagaki Y
AD  - Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
FAU - Mizuno, Shohei
AU  - Mizuno S
AD  - Division of Hematology, Department of Internal Medicine, Aichi Medical 
      University, Nagakute, Japan.
FAU - Nishio, Nobuhiro
AU  - Nishio N
AD  - Center for Advanced Medicine and Clinical Research, Department of Advanced 
      Medicine, Nagoya University Hospital, Nagoya, Japan.
AD  - Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Katsuyama, Naoya
AU  - Katsuyama N
AD  - Department of Immunology, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
FAU - Sato, Yoshie
AU  - Sato Y
AD  - Department of Immunology, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
FAU - Kobayashi, Miki
AU  - Kobayashi M
AD  - Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.
FAU - Ozeki, Kazutaka
AU  - Ozeki K
AD  - Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, 
      Japan.
FAU - Iida, Hiroatsu
AU  - Iida H
AD  - Department of Hematology, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
FAU - Tomita, Akihiro
AU  - Tomita A
AD  - Department of Hematology, Fujita Health University School of Medicine, Toyoake, 
      Japan.
FAU - Sawa, Masashi
AU  - Sawa M
AD  - Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
FAU - Demachi-Okamura, Ayako
AU  - Demachi-Okamura A
AD  - Division of Translational Oncoimmunology, Aichi Cancer Center Research Institute, 
      Nagoya, Japan.
FAU - Takahashi, Yoshiyuki
AU  - Takahashi Y
AD  - Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Nishikawa, Hiroyoshi
AU  - Nishikawa H
AD  - Department of Immunology, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
AD  - Division of Cancer Immunology, Research Institute/Exploratory Oncology Research 
      and Clinical Trial Center (EPOC), National Cancer Center, Tokyo, Japan.
FAU - Akatsuka, Yoshiki
AU  - Akatsuka Y
AUID- ORCID: 0000-0003-3623-2826
AD  - Department of Immunology, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan. yakatsuk@med.nagoya-u.ac.jp.
LA  - eng
GR  - 21K08369/Japan Society for the Promotion of Science/
GR  - JP21ek0510027/Japan Agency for Medical Research and Development/
PT  - Journal Article
DEP - 20230613
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (HLA-DPB1 antigen)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Humans
MH  - CD4-Positive T-Lymphocytes
MH  - *Leukemia
MH  - HLA-DP beta-Chains/genetics/metabolism
MH  - Transplantation, Homologous
MH  - *Hematopoietic Stem Cell Transplantation/methods
MH  - Receptors, Antigen, T-Cell/genetics/metabolism
MH  - *Graft vs Host Disease
OTO - NOTNLM
OT  - Allogeneic transplantation
OT  - HLA-DPB1
OT  - Leukemia
OT  - Relapse
OT  - TCR-T
EDAT- 2023/06/13 13:12
MHDA- 2023/07/21 06:43
CRDT- 2023/06/13 11:11
PHST- 2023/04/27 00:00 [received]
PHST- 2023/05/23 00:00 [accepted]
PHST- 2023/05/23 00:00 [revised]
PHST- 2023/07/21 06:43 [medline]
PHST- 2023/06/13 13:12 [pubmed]
PHST- 2023/06/13 11:11 [entrez]
AID - 10.1007/s12185-023-03621-y [pii]
AID - 10.1007/s12185-023-03621-y [doi]
PST - ppublish
SO  - Int J Hematol. 2023 Aug;118(2):252-266. doi: 10.1007/s12185-023-03621-y. Epub 
      2023 Jun 13.