Open Access

Construction of an anti‑programmed death‑ligand 1 chimeric antigen receptor and determination of its antitumor function with transduced cells

  • Authors:
    • Jiasen Xie
    • Zishan Zhou
    • Shunchang Jiao
    • Xiaokun Li
  • View Affiliations

  • Published online on: May 2, 2018     https://doi.org/10.3892/ol.2018.8617
  • Pages: 157-166
  • Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A chimeric antigen receptor (CAR) is a type of fusion protein that comprises an antigen‑recognition domain and signaling domains. In the present study, a programmed death‑ligand 1 (PD‑L1)‑specific CAR, comprised of a single‑chain variable fragment (scFv) derived from a monoclonal antibody, co‑stimulatory domains of cluster of differentiation (CD) 28 and 4‑1BB and a T‑cell‑activation domain derived from CD3ζ, was designed. The construction was cloned and packaged into the lentiviral vector pLVX. Flow cytometry confirmed that peripheral blood mononuclear cells were efficiently transduced and that the CAR was successfully expressed on T cells. The cytotoxicity of transduced T cells was detected using PD‑L1‑positive NCI‑H358 bronchioalveolar carcinoma cells and A549 lung adenocarcinoma cells (with a low expression of PD‑L1, only in the A549 cells). The results demonstrated mild cytotoxicity at an effector‑to‑target ratio of 10:1. An ELISA revealed a significant increase in the level of interferon‑γ released from T cells transduced with scFv‑28Bz when the cells were co‑cultured with PD‑L1‑positive NCI‑H358 cells, while interkeukin‑2 and tumor necrosis factor‑α levels remained unchanged. These data indicated a potential method for the treatment of solid tumors.
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July-2018
Volume 16 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Xie J, Zhou Z, Jiao S and Li X: Construction of an anti‑programmed death‑ligand 1 chimeric antigen receptor and determination of its antitumor function with transduced cells. Oncol Lett 16: 157-166, 2018
APA
Xie, J., Zhou, Z., Jiao, S., & Li, X. (2018). Construction of an anti‑programmed death‑ligand 1 chimeric antigen receptor and determination of its antitumor function with transduced cells. Oncology Letters, 16, 157-166. https://doi.org/10.3892/ol.2018.8617
MLA
Xie, J., Zhou, Z., Jiao, S., Li, X."Construction of an anti‑programmed death‑ligand 1 chimeric antigen receptor and determination of its antitumor function with transduced cells". Oncology Letters 16.1 (2018): 157-166.
Chicago
Xie, J., Zhou, Z., Jiao, S., Li, X."Construction of an anti‑programmed death‑ligand 1 chimeric antigen receptor and determination of its antitumor function with transduced cells". Oncology Letters 16, no. 1 (2018): 157-166. https://doi.org/10.3892/ol.2018.8617