›› 2020, Vol. 40 ›› Issue (1): 37-.doi: 10.3969/j.issn.1674-8115.2020.01.006

• Original article (Basic research) • Previous Articles     Next Articles

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   

  1. 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:2020-01-28 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.

Key words: programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1) inhibitor, humanized immunity, patient-derived xenograft model (PDX model), lung cancer