PMID- 29556312
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 15
IP  - 4
DP  - 2018 Apr
TI  - PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects 
      in breast cancer.
PG  - 5924-5932
LID - 10.3892/ol.2018.8075 [doi]
AB  - Placenta-specific 1 (PLAC1), a novel cancer-testis antigen (CTA), is expressed in 
      a number of different human malignancies. It is frequently produced in breast 
      cancer, serving a function in tumorigenesis. Adoptive immunotherapy using T cell 
      receptor (TCR)-engineered T cells against CTA mediates objective tumor 
      regression; however, to the best of our knowledge, targeting PLAC1 using 
      engineered T cells has not yet been attempted. In the present study, the cDNAs 
      encoding TCRalpha- and beta-chains specific for human leukocyte antigen 
      (HLA)-A*0201-restricted PLAC1 were cloned from a cytotoxic T-lymphocyte, 
      generated by in vitro by the stimulation of CD8+ T cells using autologous HLA-A2+ 
      dendritic cells loaded with a PLAC1-specific peptide (p28-36, VLCSIDWFM). The 
      TCRalpha/beta-chains were linked by a 2A peptide linker (TCRalpha-Thosea asigna virus-TCRbeta), 
      and the constructs were cloned into the lentiviral vector, followed by 
      transduction into human cytotoxic (CD8+) T cells. The efficiency of transduction 
      was up to 25.16%, as detected by PLAC1 multimers. TCR-transduced CD8+ T cells, 
      co-cultured with human non-metastatic breast cancer MCF-7 cells (PLAC1+, HLA-A2+) 
      and triple-negative breast cancer MDAMB-231 cells (PLAC1+, HLA-A2+), produced 
      interferon gamma and tumor necrosis factor alpha, suggesting TCR activation. Furthermore, 
      the PLAC1 TCR-transduced CD8+ T cells efficiently and specifically identified and 
      annihilated the HLA-A2+/PLAC1+ breast cancer cell lines in a lactate 
      dehydrogenase activity assay. Western blot analysis demonstrated that TCR 
      transduction stimulated the production of mitogen-activated protein kinase 
      signaling molecules, extracellular signal-regulated kinases 1/2 and nuclear 
      factor-kappaB, through phosphoinositide 3-kinase gamma-mediated phosphorylation of 
      protein kinase B in CD8+ T cells. Xenograft mouse assays revealed that PLAC1 
      TCR-transduced CD8+T cells significantly delayed the tumor progression in 
      mice-bearing breast cancer compared with normal saline or negative 
      control-transduced groups. In conclusion, a novel HLA-A2-restricted and 
      PLAC1-specific TCR was identified. The present study demonstrated PLAC1 to be a 
      potential target for breast cancer treatment; and the usage of PLAC1-specific 
      TCR-engineered T cells may be a novel strategy for PLAC1-positive breast cancer 
      treatment.
FAU - Li, Qiongshu
AU  - Li Q
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
AD  - Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and 
      Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, 
      Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
FAU - Liu, Muyun
AU  - Liu M
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Wu, Man
AU  - Wu M
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Zhou, Xin
AU  - Zhou X
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Wang, Shaobin
AU  - Wang S
AD  - Interventional and Minimally Invasive Oncology Therapy Department, Peking 
      University Shenzhen Hospital, Shenzhen, Guangdong 518035, P.R. China.
FAU - Hu, Yuan
AU  - Hu Y
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Wang, Youfu
AU  - Wang Y
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - He, Yixin
AU  - He Y
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Zeng, Xiaoping
AU  - Zeng X
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Chen, Junhui
AU  - Chen J
AD  - Interventional and Minimally Invasive Oncology Therapy Department, Peking 
      University Shenzhen Hospital, Shenzhen, Guangdong 518035, P.R. China.
FAU - Liu, Qubo
AU  - Liu Q
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Xiao, Dong
AU  - Xiao D
AD  - Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and 
      Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, 
      Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
FAU - Hu, Xiang
AU  - Hu X
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
FAU - Liu, Weibin
AU  - Liu W
AD  - Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180216
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC5844056
OTO - NOTNLM
OT  - T cell receptor
OT  - breast cancer
OT  - cancer immunotherapy
OT  - cytotoxic T cells
OT  - placenta specific 1
EDAT- 2018/03/21 06:00
MHDA- 2018/03/21 06:01
PMCR- 2018/02/16
CRDT- 2018/03/21 06:00
PHST- 2017/05/10 00:00 [received]
PHST- 2017/12/11 00:00 [accepted]
PHST- 2018/03/21 06:00 [entrez]
PHST- 2018/03/21 06:00 [pubmed]
PHST- 2018/03/21 06:01 [medline]
PHST- 2018/02/16 00:00 [pmc-release]
AID - OL-0-0-8075 [pii]
AID - 10.3892/ol.2018.8075 [doi]
PST - ppublish
SO  - Oncol Lett. 2018 Apr;15(4):5924-5932. doi: 10.3892/ol.2018.8075. Epub 2018 Feb 
      16.