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Article

PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer

  • Authors:
    • Qiongshu Li
    • Muyun Liu
    • Man Wu
    • Xin Zhou
    • Shaobin Wang
    • Yuan Hu
    • Youfu Wang
    • Yixin He
    • Xiaoping Zeng
    • Junhui Chen
    • Qubo Liu
    • Dong Xiao
    • Xiang Hu
    • Weibin Liu
  • View Affiliations / Copyright

    Affiliations: Shenzhen Beike Cell Engineering Research Institute, Shenzhen, Guangdong 518057, P.R. China, Interventional and Minimally Invasive Oncology Therapy Department, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518035, P.R. China, 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
  • Pages: 5924-5932
    |
    Published online on: February 16, 2018
       https://doi.org/10.3892/ol.2018.8075
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Abstract

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 TCRα‑ and β‑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 TCRα/β‑chains were linked by a 2A peptide linker (TCRα‑Thosea asigna virus‑TCRβ), 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 γ and tumor necrosis factor α, 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‑κB, through phosphoinositide 3‑kinase γ‑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.
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Copy and paste a formatted citation
Spandidos Publications style
Li Q, Liu M, Wu M, Zhou X, Wang S, Hu Y, Wang Y, He Y, Zeng X, Chen J, Chen J, et al: PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncol Lett 15: 5924-5932, 2018.
APA
Li, Q., Liu, M., Wu, M., Zhou, X., Wang, S., Hu, Y. ... Liu, W. (2018). PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncology Letters, 15, 5924-5932. https://doi.org/10.3892/ol.2018.8075
MLA
Li, Q., Liu, M., Wu, M., Zhou, X., Wang, S., Hu, Y., Wang, Y., He, Y., Zeng, X., Chen, J., Liu, Q., Xiao, D., Hu, X., Liu, W."PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer". Oncology Letters 15.4 (2018): 5924-5932.
Chicago
Li, Q., Liu, M., Wu, M., Zhou, X., Wang, S., Hu, Y., Wang, Y., He, Y., Zeng, X., Chen, J., Liu, Q., Xiao, D., Hu, X., Liu, W."PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer". Oncology Letters 15, no. 4 (2018): 5924-5932. https://doi.org/10.3892/ol.2018.8075
Copy and paste a formatted citation
x
Spandidos Publications style
Li Q, Liu M, Wu M, Zhou X, Wang S, Hu Y, Wang Y, He Y, Zeng X, Chen J, Chen J, et al: PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncol Lett 15: 5924-5932, 2018.
APA
Li, Q., Liu, M., Wu, M., Zhou, X., Wang, S., Hu, Y. ... Liu, W. (2018). PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Oncology Letters, 15, 5924-5932. https://doi.org/10.3892/ol.2018.8075
MLA
Li, Q., Liu, M., Wu, M., Zhou, X., Wang, S., Hu, Y., Wang, Y., He, Y., Zeng, X., Chen, J., Liu, Q., Xiao, D., Hu, X., Liu, W."PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer". Oncology Letters 15.4 (2018): 5924-5932.
Chicago
Li, Q., Liu, M., Wu, M., Zhou, X., Wang, S., Hu, Y., Wang, Y., He, Y., Zeng, X., Chen, J., Liu, Q., Xiao, D., Hu, X., Liu, W."PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer". Oncology Letters 15, no. 4 (2018): 5924-5932. https://doi.org/10.3892/ol.2018.8075
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