PMID- 36589698
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231103
IS  - 2372-7705 (Print)
IS  - 2372-7705 (Electronic)
IS  - 2372-7705 (Linking)
VI  - 28
DP  - 2023 Mar 16
TI  - A library of cancer testis specific T cell receptors for T cell receptor gene 
      therapy.
PG  - 1-14
LID - 10.1016/j.omto.2022.11.007 [doi]
AB  - To increase the number of cancer patients that can be treated with T cell 
      receptor (TCR) gene therapy, we aimed to identify a set of high-affinity 
      cancer-specific TCRs targeting different melanoma-associated antigens (MAGEs). In 
      this study, peptides derived from MAGE genes with tumor-specific expression 
      pattern were identified by human leukocyte antigen (HLA) peptidomics. Next, 
      peptide-HLA tetramers were generated, and used to sort MAGE-specific CD8(+) 
      T cell clones from the allogeneic (allo) HLA repertoire of healthy donors. To 
      evaluate the clinical potential, most potent TCRs were sequenced, transferred 
      into peripheral blood-derived CD8(+) T cells, and tested for antitumor efficacy. 
      In total we identified, seven MAGE-specific TCRs that effectively target MAGE-A1, 
      MAGE-A3, MAGE-A6, and MAGE-A9 in the context of HLA-A *01:01, -A *02:01, -A *03:01, 
      -B *07:02, -B *35:01, or -C *07:02. TCR gene transfer into CD8(+) T cells resulted in 
      efficient reactivity against a variety of different tumor types, while no 
      cross-reactivity was detected. In addition, major in vivo antitumor effects of 
      MAGE-A1 specific TCR engineered CD8(+) T cells were observed in the orthotopic 
      xenograft model for established multiple myeloma. The identification of seven 
      MAGE-specific TCRs expands the pool of cancer patients eligible for TCR gene 
      therapy and increases possibilities for personalized TCR gene therapy.
CI  - (c) 2022 The Author(s).
FAU - de Rooij, Marije A J
AU  - de Rooij MAJ
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Remst, Dennis F G
AU  - Remst DFG
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - van der Steen, Dirk M
AU  - van der Steen DM
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Wouters, Anne K
AU  - Wouters AK
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Hagedoorn, Renate S
AU  - Hagedoorn RS
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Kester, Michel G D
AU  - Kester MGD
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Meeuwsen, Miranda H
AU  - Meeuwsen MH
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Wachsmann, Tassilo L A
AU  - Wachsmann TLA
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - de Ru, Arnoud H
AU  - de Ru AH
AD  - Center for Proteomics and Metabolics, Leiden University Medical Center, 2333 ZA 
      Leiden, the Netherlands.
FAU - van Veelen, Peter A
AU  - van Veelen PA
AD  - Center for Proteomics and Metabolics, Leiden University Medical Center, 2333 ZA 
      Leiden, the Netherlands.
FAU - Verdegaal, Els M E
AU  - Verdegaal EME
AD  - Department of Medical Oncology, Oncode Institute, Leiden University Medical 
      Center, 2333 ZA Leiden, the Netherlands.
FAU - Falkenburg, J H Frederik
AU  - Falkenburg JHF
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
FAU - Heemskerk, Mirjam H M
AU  - Heemskerk MHM
AD  - Department of Hematology, Leiden University Medical Center, Albinusdreef 2, 2333 
      ZA Leiden, the Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20221202
PL  - United States
TA  - Mol Ther Oncolytics
JT  - Molecular therapy oncolytics
JID - 101666776
EIN - Mol Ther Oncolytics. 2023 Oct 23;31:100738. PMID: 37920174
PMC - PMC9792401
OTO - NOTNLM
OT  - CD8+ T cells
OT  - Cancer Testis genes
OT  - MAGE
OT  - T cell receptor
OT  - TCR gene therapy
COIS- The authors report no competing interests.
EDAT- 2023/01/03 06:00
MHDA- 2023/01/03 06:01
PMCR- 2022/12/02
CRDT- 2023/01/02 04:04
PHST- 2022/06/08 00:00 [received]
PHST- 2022/11/29 00:00 [accepted]
PHST- 2023/01/02 04:04 [entrez]
PHST- 2023/01/03 06:00 [pubmed]
PHST- 2023/01/03 06:01 [medline]
PHST- 2022/12/02 00:00 [pmc-release]
AID - S2372-7705(22)00142-5 [pii]
AID - 10.1016/j.omto.2022.11.007 [doi]
PST - epublish
SO  - Mol Ther Oncolytics. 2022 Dec 2;28:1-14. doi: 10.1016/j.omto.2022.11.007. 
      eCollection 2023 Mar 16.