Original article (Basic research)

Establishment of a lung cancer momodel with humanized immunity and its role in efficacy evaluation of programmed death-1 inhibitors

  • ZHOU Zhen ,
  • XU Yun-hua ,
  • ZHANG Fei-fei ,
  • ZHAO Yi ,
  • GUO Lin ,
  • FU Guo-long ,
  • SHEN Sheng-ping ,
  • LENG Xue-jiao
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  • 1. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China; 2. Shanghai Lide Biotechnology Co. Ltd., Shanghai 201203, China

Online published: 2020-03-05

Supported by

Scientific Research Program of Science and Technology Commission of Shanghai Municipality (16140902800).

Abstract

Objective · To establish a lung cancer momodel with humanized peripheral blood mononuclear cells (PBMC) expressing programmed death-ligand 1 (PD-L1), and study the role of the model in evaluating the efficacy of programmed death-1 (PD-1) inhibitors. Methods · Fresh biopsy tissue samples or tumor cells in malignant pleural effusion the patients with advanced non-small cell lung cancer were inoculated subcutaneously in CB17-SCID mice to establish patient-derived xenograft (PDX) models. The of PD-L1 in PDX models was detectedimmunohistochemistry. The mature human PBMC and PDX model tumor cells were mixed and then inoculated into NCG mice to establish a PDX model of lung cancer with humanized immunity, on which the efficacy of PD-1 inhibitor was verified. Results · Among the PDX models established16 clinical samples, 2 were strongly positive for PD-L1, 4 were positive, and the rest were negative. In the PDX model with strongly positive PD-L1, the tumor growth inhibition rate of cindilimab, an inhibitor of PD-1, was 82.6%, 21 days after the initial administration; in the PDX model with negative PD-L1, the inhibitor of PD-1 showed no antitumor activity. Conclusion · A PD-L1-expressing lung cancer momodel with humanized immunity is successfully established and the efficacy of PD-1 inhibitor can be evaluated on the model.

Cite this article

ZHOU Zhen , XU Yun-hua , ZHANG Fei-fei , ZHAO Yi , GUO Lin , FU Guo-long , SHEN Sheng-ping , LENG Xue-jiao . Establishment of a lung cancer momodel with humanized immunity and its role in efficacy evaluation of programmed death-1 inhibitors[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2020 , 40(1) : 37 . DOI: 10.3969/j.issn.1674-8115.2020.01.006

Outlines

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