PMID- 38243600
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240315
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 32
IP  - 3
DP  - 2024 Mar 6
TI  - Preclinical evaluation of a novel CAR-T therapy utilizing a scFv antibody highly 
      specific to MAGE-A4(p230-239)/HLA-A *02:01 complex.
PG  - 734-748
LID - S1525-0016(24)00018-2 [pii]
LID - 10.1016/j.ymthe.2024.01.018 [doi]
AB  - Despite the revolutionary success of chimeric antigen receptor (CAR)-T therapy 
      for hematological malignancies, successful CAR-T therapies for solid tumors 
      remain limited. One major obstacle is the scarcity of tumor-specific cell-surface 
      molecules. One potential solution to overcome this barrier is to utilize 
      antibodies that recognize peptide/major histocompatibility complex (MHCs) in a 
      T cell receptor (TCR)-like fashion, allowing CAR-T cells to recognize 
      intracellular tumor antigens. This study reports a highly specific single-chain 
      variable fragment (scFv) antibody against the MAGE-A4(p230-239)/human leukocyte 
      antigen (HLA)-A *02:01 complex (MAGE-A4 pMHC), screened from a human scFv phage 
      display library. Indeed, retroviral vectors encoding CAR, utilizing this scFv 
      antibody as a recognition component, efficiently recognized and lysed MAGA-A4(+) 
      tumor cells in an HLA-A *02:01-restricted manner. Additionally, the adoptive 
      transfer of T cells modified by the CAR-containing glucocorticoid-induced tumor 
      necrosis factor receptor (TNFR)-related receptor (GITR) intracellular domain 
      (ICD), but not CD28 or 4-1BB ICD, significantly suppressed the growth of 
      MAGE-A4(+) HLA-A *02:01(+) tumors in an immunocompromised mouse model. Of note, a 
      comprehensive analysis revealed that a broad range of amino acid sequences of the 
      MAGE-A4p(230-239) peptide were critical for the recognition of MAGE-A4 pMHC by 
      these CAR-T cells, and no cross-reactivity to analogous peptides was observed. 
      Thus, MAGE-A4-targeted CAR-T therapy using this scFv antibody may be a promising 
      and safe treatment for solid tumors.
CI  - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Wang, Linan
AU  - Wang L
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan.
FAU - Matsumoto, Masahiro
AU  - Matsumoto M
AD  - Tokyo Laboratory 11, R&D Center, Sony Group Corporation, Bunkyo-ku, Tokyo 
      113-8510, Japan.
FAU - Akahori, Yasushi
AU  - Akahori Y
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan; Center for Comprehensive Cancer 
      Immunotherapy, Mie University, Tsu, Mie 514-8507, Japan.
FAU - Seo, Naohiro
AU  - Seo N
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan.
FAU - Shirakura, Kazuko
AU  - Shirakura K
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan.
FAU - Kato, Takuma
AU  - Kato T
AD  - Department of Cellular and Molecular Immunology, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan.
FAU - Katsumoto, Yoichi
AU  - Katsumoto Y
AD  - Tokyo Laboratory 11, R&D Center, Sony Group Corporation, Bunkyo-ku, Tokyo 
      113-8510, Japan.
FAU - Miyahara, Yoshihiro
AU  - Miyahara Y
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan; Center for Comprehensive Cancer 
      Immunotherapy, Mie University, Tsu, Mie 514-8507, Japan. Electronic address: 
      miyahr-y@med.mie-u.ac.jp.
FAU - Shiku, Hiroshi
AU  - Shiku H
AD  - Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, Tsu, Mie 514-8507, Japan; Center for Comprehensive Cancer 
      Immunotherapy, Mie University, Tsu, Mie 514-8507, Japan. Electronic address: 
      shiku@med.mie-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20240118
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Single-Chain Antibodies)
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (HLA-A Antigens)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - *Single-Chain Antibodies/genetics
MH  - *Receptors, Chimeric Antigen/genetics
MH  - T-Lymphocytes
MH  - HLA-A Antigens
MH  - Immunotherapy, Adoptive
MH  - *Neoplasms
PMC - PMC10928314
OTO - NOTNLM
OT  - CAR
OT  - GITR
OT  - ICD
OT  - MAGE-A4 peptide
OT  - MHC complex
OT  - pMHC
COIS- Declaration of interests M.M. and Y.K. are employees of Sony Group Corporation, 
      which collaborated in the development of a closed-cell isolation system. The 
      Department of Personalized Cancer Immunotherapy, Mie University Graduate School 
      of Medicine, is an endowment department supported by a grant from T cell Nouveau.
EDAT- 2024/01/20 10:42
MHDA- 2024/03/11 06:43
PMCR- 2025/03/06
CRDT- 2024/01/20 01:36
PHST- 2023/04/25 00:00 [received]
PHST- 2023/09/30 00:00 [revised]
PHST- 2024/01/12 00:00 [accepted]
PHST- 2025/03/06 00:00 [pmc-release]
PHST- 2024/03/11 06:43 [medline]
PHST- 2024/01/20 10:42 [pubmed]
PHST- 2024/01/20 01:36 [entrez]
AID - S1525-0016(24)00018-2 [pii]
AID - 10.1016/j.ymthe.2024.01.018 [doi]
PST - ppublish
SO  - Mol Ther. 2024 Mar 6;32(3):734-748. doi: 10.1016/j.ymthe.2024.01.018. Epub 2024 
      Jan 18.