rmhTNF-α联合PD-1单抗治疗小鼠Lewis肺癌的研究

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Abstract Objective To study the therapeutic effect and mechanism of recombinant mutated human tumor necrosis factor-α (rmhTNF-α) combined with PD-1 monoclonal antibody (anti-PD-1) in Lewis lung cancer in mice. Methods A total of 24 female C57BL/6 mice aged 6 to 8 weeks were divided into 4 groups according to the random number table method, with 6 mice in each group: normal saline group, rmhTNF-group, anti-PD-1 group, and combined administration group. The tumor was measured with vernier caliper and observed by in vivo imaging. After 16 days, the mice were euthanized and the tumor was removed and weighed. The survival period of mice were observed. Immunohistochemical was used to detect tumor CD8+T cells. Results Compared with the normal saline group, the tumor volume and tumor weight in the rmhTNF-α group, anti-PD-1 group and the combined administration group all decreased, with highly statistically significant differences (P ＜ 0.01). The tumor volume of rmhTNF-α group was larger than that of the combined administration group, and the difference was statistically significant (P ＜ 0.05). However, there was no significant difference in tumor volume between the combined administration group and the anti-PD-1 group (P ＞ 0.05). There was no statistically significant difference in tumor weight between the combined administration group and the rmhTNF-α group and anti-PD-1 group (all P ＞ 0.05). Compared with the normal saline group, the survival of rmhTNF-α group, anti-PD-1 group and the combined administration group increased, and the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01), while the survival of the combined administration group was not statistically significant compared with the rmhTNF-α group and anti-PD-1 group (all P ＞ 0.05). Compared with the normal saline group, the number of CD8+T cells increased in the rmhTNF-α group (P ＜ 0.05). Compared with the normal saline group, the number of CD8+T cells increased significantly in the anti-PD-1 group and combined administration group (P ＜ 0.01). The number of CD8+T cells in the combined administration group was less than that in the rmhTNF-α group (P ＜ 0.01), while the number of CD8+T cells was not statistically significant compared with that in the anti-PD-1 group (P ＞ 0.05). Conclusion RmhTNF-α can inhibit lung cancer in mice, but it can not enhance the effect of anti-PD-1 to treat lung cancer.

Key words： Recombinant mutated human tumor necrosis factor-α PD-1 monoclonal antibody CD8+T cell Lewis lung cancer

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	ZHU Liaoliao ZHANG Cun XU Ying LI Xiaoju GAO Yuan HAN Jun ZHANG Yingqi

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ZHU Liaoliao ZHANG Cun XU Ying LI Xiaoju GAO Yuan HAN Jun ZHANG Yingqi. Study of rmhTNF-α combined with anti-PD-1 in the treatment of Lewis lung cancer in mice[J]. 中国医药导报, 2020, 17(10): 4-7.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2020/V17/I10/4

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