Establishment of a lung cancer mouse model with humanized immunity and its role in efficacy evaluation of programmed death-1 inhibitors / 上海交通大学学报（医学版）

ABSTRACT

Objective:To establish a lung cancer mouse model 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 from the patients with advanced non-small cell lung cancer were inoculated subcutaneously in CB17-SCID mice to establish patient-derived xenograft (PDX) models. The expression of PD-L1 in PDX models was detected by immunohistochemistry. 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 established by 16 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 mouse model with humanized immunity is successfully established and the efficacy of PD-1 inhibitor can be evaluated on the model.