异种抗原瘤内注射对荷瘤小鼠肿瘤生长的抑制作用

Antitumor efficacy of intratumoral injection of xenoantigen in mice

背景:异种抗原的免疫原性比较强,容易引起较强的免疫应答。如果将异种抗原直接引入肿瘤内部,在肿瘤内部引发一系列免疫反应,有可能逆转肿瘤微环境的免疫抑制状态,达到抗肿瘤的目的。目的:评价人红细胞膜抗原瘤内注射对荷S180肉瘤小鼠肿瘤生长的抑制作用。方法:复制昆明小鼠S180肉瘤皮下瘤模型,瘤内注射质量浓度为5g/L的人红细胞膜抗原或生理盐水,连续注射5d,记录注射前及注射第3,7,14天肿瘤体积变化。同时设肿瘤细胞与人红细胞膜抗原同时接种组、免疫后瘤内注射人红细胞膜抗原组、免疫后瘤内注射生理盐水组。另取60只小鼠复制S180肉瘤皮下瘤模型,免疫及瘤内注射人红细胞膜抗原或生理盐水同前。注射第14天每组处死6只小鼠,肿瘤称质量,行病理学分析,每组剩余小鼠继续观察生存情况。结果与结论:各组小鼠肿瘤体积逐渐增大,第14天人红细胞膜抗原与肿瘤细胞同时接种组、免疫后人红细胞膜抗原瘤内注射组、人红细胞膜抗原瘤内注射组肿瘤体积均小于瘤内注射生理盐水组。瘤内注射人红细胞膜抗原可显著降低肿瘤质量。瘤内注射人红细胞膜抗原后镜下可见肿瘤细胞坏死、淋巴细胞等炎症细胞浸润。未观察到各组小鼠生存期有明显差别。结果表明异种红细胞膜抗原瘤内注射可以抑制小鼠S180肉瘤肿瘤生长。

BACKGROUND：Herterologous antigen has strong immunogenicity and easily induces immunological response.Introduction of herterologous antigen into tumor may induce a serial of immunological reactions in the tumor and may reverse the immunosuppression of tumor microenvironment to treat tumor.OBJECTIVE：To evaluate the antitumor efficacy of intratumoral injection of human erythrocyte membrane antigens in mice bearing S180 sarcoma.METHODS：Kunming mice bearing S180 sarcoma model were established and treated with 5 g/L human erythrocyte membrane antigens suspension or normal saline for five days.Tumor volume was calculated before the first injection and 3,7,and 14 days after the first injection.In addition,the tumor cells in combination with human erythrocyte membrane antigens group,the injection of saline group（the control group）,and the injection of human erythrocyte membrane antigens or saline group（pre-immunized by suspension of human erythrocyte of blood group type A）.Another 60 mice bearing S180 sarcoma were established and subjected to the above pre-immunization and injection of saline or human erythrocyte membrane antigens.Six mice selected from each group were sacrificed 14 days after the first injection,and tumors were weighed,followed by histological examination.Survival of remainders in each group was observed.RESULTS AND CONCLUSION：Tumor volumes in each group increased gradually.Tumor volumes in the human erythrocyte membrane antigens injection group,the tumor cells in combination with human erythrocyte membrane antigens group,and the human erythrocyte membrane antigens injection group（immunized）were smaller than the control group,Intratumoral injection of human erythrocyte membrane antigens significantly reduced tumor weights.Tumor necrosis,infiltration of inflammatory cells such as lymphocytes were observed in tumor tissues section examination following the intratumoral injection of human erythrocyte membrane antigens.The mouse survival time showed no statistical difference among different groups.Intratumoral injection of heterologous erythrocyte membrane antigens can inhibit tumor growth of S180 sarcoma bearing mice.