PD-1抗体在小鼠胰腺癌中的治疗作用

Therapeutic effect of PD-1antibody on pancreatic cancer in mice

目的评价PD-1抗体在小鼠原位胰腺癌中的治疗作用。方法将6～8w的C57小鼠采用原位注射Pan02细胞的方式构建原位胰腺癌模型，同时构建皮下瘤模型。将C57小鼠随机分为2组（PD-1抗体组和观察组）。PD-1抗体采用腹腔注射的方式，200ug/只，观察组给予同等剂量的PBS。间隔5d给予一次，共行3次治疗。治疗结束后1w评价肿瘤的大小、CD8+T细胞的数目、血清中IFN-γ的水平，同时观察2组的生存期。结果2组小鼠瘤体的重量分别为（0.77±0.05）g和（1.44±0.07）g（P＜0.01）。外周血中CD8+T细胞的数量分别为（27.96±1.84）%和（19.38±1.15）%（P＜0.01）。肿瘤组织中CD8+T细胞的数量分别为（34.80±3.29）%和（22.45±1.78）%（P＜0.01）。PD-1抗体组和PBS组小鼠血清中IFN-γ水平也存在统计学差异，分别为（39.01±3.08）pg/mL和（15.78±2.26）pg/mL（P＜0.01）。PD-1抗体组小鼠的中位生存时间为52.6d（95%CI：48.4～5.76），而PBS组小鼠的中位生存时间为39.1d（95%CI：36.1～42.1）（P＜0.01）。结论PD-1抗体能够增加外周血及肿瘤组织中的CD8+T细胞，并能够抑制小鼠原位胰腺癌的生长，且延长生存期。

Objective To evaluate the therapeutic effect of PD-1antibody in mouse with pancreatic carcinoma.Methods In situ and subcutaneous pancreatic cancer models were constructed by injecting pan02cells into6-8week C57mice.The C57mice were randomly divided into two groups,the PD-1antibody group and the observation group.PD-1antibody group was injected intraperitoneally at200ug/mouse every5days for a total of3times,and the observation group was given equal volume of PBS.One week after treatment,size of tumor,number of CD8+cells,serum IFN-γlevel,and survival time in the two groups were observed.Results Tumor weight in the two groups were(0.77±0.05)g and(1.44±0.07)g respectively(P<0.01).Number of CD8+T cells was(27.96±1.84)%and(19.38±1.15)%respectively in peripheral blood(P<0.01),and(34.80±3.29)%and(22.45±1.78)%respectively in tumor tissue.IFN-γlevel also showed significant difference between the two groups,(39.01±3.08)pg/mL in the PD-1group vs(15.78±2.26)pg/mL in the PBS group,P<0.01.Median survival time was52.6days(95%CI:48.4-57.6)in the PD-1antibody group,and39.1days(95%CI:36.1-42.1)in the PBS group(P<0.01).Conclusion PD-1antibody significantly increased number of CD8+T cells in both peripheral blood and tumor tissue,inhibited growth of in situ pancreatic cancer in mouse,and extended survival time.