目的 研究免疫细胞治疗产品扩增活化的淋巴细胞（EAL）是否具有成瘤性，为其临床应用提供安全性依据。方法 采用BALB/c裸鼠，分为溶媒对照组、阳性对照（Hela细胞）组、EAL低、高剂量（1×10⁷、5×10⁷/只）组，sc给药1次，观察裸鼠临床症状、注射部位有无结节或肿物形成；每周2次称动物体质量；测量肿物体积，绘制生长曲线；肿物组织取出后，HE染色，光镜下进行病理检查。结果 注射后1周内，阳性对照组注射部位均有肿物生长，随着时间的延长体积逐渐增大；自给药后20 d起，阳性对照组雌性裸鼠与溶媒对照组比较，体质量显著增加（P<0.05、0.01），但身体明显消瘦；病理学检查发现，阳性对照组皮下肿瘤细胞灶状/巢状/团块状增生，肿瘤组织坏死伴炎性细胞浸润、伴或不伴有真皮炎性细胞浸润及出血。EAL低、高剂量组临床症状观察和组织病理学检测均未见肿瘤样病变，体质量增长趋势与溶媒对照组一致。结论 BALB/c裸鼠sc EAL不具有成瘤性。

Objective To study the tumorigenicity of expanded activated lymphocytes (EAL) from immunocyte therapy products and to provide safety data for its clinical application.Methods Total of 80 BALB/c nude mice were divided into four groups:negative control, positive control (Hela cells), EAL low-dose and high-dose group (1×10⁷ and 5×10⁷ cells per mouse). Cells were injected subcutaneously once to observe the clinical symptoms of the formation of nodules or masses in the injection site of nude mice. Animal weight was weighed two times a week; The volume of tumors was measured to plot growth curve. It would be confirmed whether the cancer or metastatic tumor form through the pathological examination after HE staining.Results The Hela cell tumor-bearing mice was constructed successfully, and the tumor formation in the positive mice group was 100%.Within one week after injection, there were masses growth in the injection site of positive control group and the volume increased gradually along with the time. Body mass of female nude mice in positive control group increased significantly compared with negative control group (P< 0.05, 0.01) 20 d after administration, but the body was much thinner. Histopathological examination revealed that the positive control group contained subcutaneous tumor cells with foci/nests/lumps like hyperplasia, tumor necrosis accompanied by infiltration of inflammatory cells, with or without infiltration and hemorrhage of true dermatitis cells,. However, neither the EAL low-dose group nor the EAL high-dose group showed tumor-like lesions in the clinical observation and histopathology, and the growth trend of body mass was consistent with that of negative control group.Conclusion The immunocyte therapy product EAL appears to be safe and without tumorigenicity in BALB/c nude mice.

十二五国家科技重大专项（2015ZX09501007-004）；国家重点研发计划课题（2016YFA0101503）；中检院学科带头人课题（2015X1）；广东省省级科技计划项目（2014B020227002）