CEA-rV治疗CEA阳性肿瘤的实验和应用研究

目的：探讨CEA重组基因痘苗病毒（CEA-rV）对实验动物CEA阳性肿瘤的预防和治疗作用。方法：1）预防组：将实验鼠分为4组．先皮下接种痘苗病毒（1、2组野生型W-VV，3、4组CEA-rV）3次，再分别皮下注射同源鼠肝癌细胞（1、3组Hepa-CEA^-，2、4组Hepa-CEA^＋）。2）治疗组：同样4组，先皮下注射肝癌细胞（1、3组Hepa-CEA^-，2、4组Hepa-CEA^＋），7d后再分别皮下接种痘苗病毒（1、2组W-VV，3、4组CEA-rV）。以后每周测量一次肿瘤大小，并观察动物反应。结果：1）预防组：接种CEA-rV／Hepa-CEA^＋组各鼠在观察期限内无肿瘤形成，而3个对照组各鼠皮下均有肿瘤形成，并且以相近速度快速增长（肿瘤体积平均3．5cm^3）。2）治疗组，接种Hepa-CEA^＋／CEA-rV组小鼠皮下肿瘤生长缓慢，瘤块较小（平均1cm^3），而3个对照组肿瘤生长迅速，瘤块较大（平均5cm^3）。无论预防组和对照组小鼠在整个实验过程中均未表现有毒副反应。结论：CEA-rV对实验性阳性肿瘤具有良好的预防和治疗作用，而且预防作用更佳。

Experimental and Clinical Study of CEA-rV on Treatment of CEA-positive Tumors

Objective:To study the preventive and therapeutic effect of CEA recombinant vaccine virus(CEA-rV)on CEA-positive tumors and evaluate its safety in a clinical application.Methods:In the prevention group(group A),40 mice were divided into 4 subgroups,which were vaccinated by subcutaneous injection(SI)with wild-type vaccinia virus(W-VV)in subgroup 1 and 2,or CEA-rV in subgroup 3 and 4 for three times at 14-day intervals.The vaccinations were then followed by SI of Hepa-CEA tumor cells in the 1st and 3rd subgroup or Hepa-CEA-tumor cells in the 2nd and 4th.In the treatment group(group B),40 mice were divided into 4 subgroups,which were vaccinated by SI with Hepa-CEA-tumor cells in the 1st and 3rd subgroup or Hepa-CEA tumor cells in the 2nd and 4th respectively.These injections were followed by SI of W-VV in the 1st and 2nd subgroup or CEA-rV in the 3rd and 4th for 3 times at 14-day intervals.The animals' response was observed weekly after injection of the tumor cells in both Group A and B.In the clinical application study,6 volunteers were vaccinated by SI with 0.5ml of CEA-rV for 3 times at 14-day intervals.The amount of serum CEA,tumor volume and the side effects were observed before and after treatment.Results:a)In Group A,the subcutaneous tumor grew rapidly at approximately the same rate(P>0.05)in all 3 control subgroups(mass about 3.5cm3),however,no tumor grew in the mice of the 4th subgroup in which CEA-rV and Hepa-CEA tumor cells were injected.B)In Group B,the subcutaneous tumors were observed in all of the control subgroups and the tumors(mass about 5cm3)grew quickly.In the tumors of the 4th subgroup that was injected with Hepa-CEA tumor cells and CEA-rV,tumors grew slowly and the tumor mass was smaller(about 1cm3)than in the other 3 subgroups,between which no statistical significant difference was found(P>0.05).The statistical difference was significant in the comparison of the fourth subgroup with the 3 control groups(P<0.01).During the testing period,no toxicity or side effects were seen in any animals of Groups A or B.The preliminary clinical results showed that CEA-rV had a fair therapeutic effect on CEA patients with colorectal cancer and lung adenocarcinoma.No toxicity or serious side effects were found in any patients.Conclusion:The results indicate that the CEA-rV has a preventive and therapeutic effect on CEA tumors.Prevention through vaccination is more effective than treatment after tumor formation,especially in patients with CEA-positive tumors.No toxicity or side effects have been found clinically.