异体淋巴细胞和自体淋巴细胞序贯局部注射对小鼠肝癌移植瘤的治疗作用

目的 探讨用异体淋巴细胞(Heterogeneic lymphocyte, HL)和自体淋巴细胞(Autogeneic lymphocyte, AL)序贯注射的抗肿瘤作用。方法 用CC3HF1小鼠作供鼠, 制备异体淋巴细胞(HL);用CB6F1小鼠作受鼠, 在受鼠腹股沟皮下组织内接种Hepa1-6细胞。用冻融法从小鼠血浆提取冷沉淀, 制成纤维蛋白胶(Fibrin glue, FG);用FG与HL或AL组合为FG-HL或FG-AL。实验治疗分两个阶段。前阶段(共15 d):用FG-HL注射到受鼠荷瘤组织表面(实验组);用FG-磷酸盐缓冲液(FG-PBS)同法注射受鼠作对照组。而后检测两组受鼠的脾淋巴细胞杀瘤细胞率和脾淋巴细胞、CD8⁺T、NK细胞数量等免疫学指标。后阶段(共10 d):从实验组、对照组中随机选出部分受鼠, 取淋巴细胞(AL)组成FG-AL分别注射到本组其余受鼠的荷瘤组织表面;治疗后剥出受鼠体内肿瘤, 比较两组的瘤体积和抑瘤率。结果 前阶段治疗后, 实验组受鼠AL的杀瘤细胞率(26.70±7.22)%明显高于对照组AL的相应值(5.70±2.68)(P＜0.01);实验组受鼠脾淋巴细胞、CD8⁺T细胞和NK细胞数量均明显高于对照组的相应值(P＜0.05)。两阶段治疗结束后, 实验组受鼠的瘤平均体积(1.20±0.33)cm³明显小于对照组的瘤平均体积(2.05±0.37)cm³(P＜0.01);实验组的抑瘤率为41.5%。结论 肿瘤局部注射FG-HL, 再注射FG-AL可明显抑制小鼠移植瘤生长, 有望成为一种抗肿瘤生物疗法。

Therapeutic effect of sequential local injection of heterogeneic lymphocytes and autologus lymphocytes on transplanted hepatocarcinoma in mice

Objective The aim of this study was to investigate the anti-tumor effect on sequential injection of heterogeneic lymphocyte(HL)and autogeneic lymphocyte(AL). Methods The HL was prepared by using CC3HF1 mice as feeders.CB6F1 mice were used as recipients, and Hepa1-6 cells were inoculated into the recepients′ groin subcutis.A cryoprecipitate was extracted from mouse plasma by freeze-thaw method to prepare fibrin Glue(FG);FG was combined with HL or AL to be FG-HL or FG-AL.The experimental treatment consisted of two stages.At first stage(15 d), FG-HL were injected on the surface of the tumor-bearing tissue of the recipients as the experimental group, and FG-phosphate buffer saline(FG-PBS)were injected on the surface of the tumor-bearing tissue of the rest recipients as the control group.The immunological factors such as tumor cell killing rate of the spleen lymphocytes and numbers of lymphocytes, CD8⁺T and NK in the two groups were detected, respectively.At later stage(10 d), a part of mice were randomly selected from the experimental and control groups, and the lymphocytes(AL)were used to form FG-AL, which were injected on the surface of tumor-bearing tissues in the rest of mice.Tumors in mice of the two groups were compared for tumor volume and tumor inhibition rate. Results The tumor cell killing rate of AL in the experimental group(26.70±7.22) was significantly higher than that in the control group(5.70±2.68)(P＜0.01).Numbers of mouse spleen lymphocytes, CD8⁺T cells and NK cells were significantly higher than the corresponding values of the control group(P＜0.05).After the two-stage treatment, the average tumor volume of the experimental group(1.20±0.33)cm³]was significantly smaller than that of control group(2.05±0.37)cm³](P＜0.01).The tumor inhibition rate in the experiment group was 41.5% when compared to the control group. Conclusion Local injections of FG-HL followed by FG-AL can significantly inhibit the growth of transplanted tumor in mice;it is expected to become an anti-tumor biological therapy.