目的 研究免疫細(xì)胞治療產(chǎn)品擴(kuò)增活化的淋巴細(xì)胞（EAL）是否具有成瘤性，為其臨床應(yīng)用提供安全性依據(jù)。方法 采用BALB/c裸鼠，分為溶媒對照組、陽性對照（Hela細(xì)胞）組、EAL低、高劑量（1×10⁷、5×10⁷/只）組，sc給藥1次，觀察裸鼠臨床癥狀、注射部位有無結(jié)節(jié)或腫物形成；每周2次稱動(dòng)物體質(zhì)量；測量腫物體積，繪制生長曲線；腫物組織取出后，HE染色，光鏡下進(jìn)行病理檢查。結(jié)果 注射后1周內(nèi)，陽性對照組注射部位均有腫物生長，隨著時(shí)間的延長體積逐漸增大；自給藥后20 d起，陽性對照組雌性裸鼠與溶媒對照組比較，體質(zhì)量顯著增加（P<0.05、0.01），但身體明顯消瘦；病理學(xué)檢查發(fā)現(xiàn)，陽性對照組皮下腫瘤細(xì)胞灶狀/巢狀/團(tuán)塊狀增生，腫瘤組織壞死伴炎性細(xì)胞浸潤、伴或不伴有真皮炎性細(xì)胞浸潤及出血。EAL低、高劑量組臨床癥狀觀察和組織病理學(xué)檢測均未見腫瘤樣病變，體質(zhì)量增長趨勢與溶媒對照組一致。結(jié)論 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.

十二五國家科技重大專項(xiàng)（2015ZX09501007-004）；國家重點(diǎn)研發(fā)計(jì)劃課題（2016YFA0101503）；中檢院學(xué)科帶頭人課題（2015X1）；廣東省省級(jí)科技計(jì)劃項(xiàng)目（2014B020227002）