【摘要】 目的 评价肿瘤浸润淋巴细胞(TIL)在重度免疫缺陷小鼠体内的毒性反应。方法 使用NOG小鼠，给予TIL细胞3次，每周1次。考察小鼠临床症状、注射部位刺激性、摄食量、体重、血液学和血清生化检查、人源细胞因子检测和组织病理学检查等，同时考察受试物在血液中的分布情况。结果 两个剂量TIL注射对小鼠注射部位、体重、摄食量、血液学、血清生化、脏器重量等指标未见明显影响。在高剂量下，雌性小鼠在恢复期结束时IFN-γ浓度升高。与受试物相关的组织病理学改变为多器官混合细胞聚集，以及胸骨和大腿骨骨髓细胞数目增多。在血液中，均可检测到CD3~+、CD3~+CD4~+、CD3~+CD8~+细胞，3种细胞变化趋势一致，且呈剂量依赖性，至末次给药后29 d，3种细胞数量基本消除。结论 NOG小鼠3次给药后，对TIL具有较好的耐受性，且在恢复期结束时TIL在小鼠血液中基本消除。更多还原

【Abstract】 Objective To determine the toxicity of tumor infiltrating lymphocytes (TIL) in mice with severe immunodeficiency.Methods NOG mice were given TIL cells three times,once a week.During the study,the clinical symptoms,food consumption,injection site observation,body weight,hematology and clinical chemistry,human cytokines and histopathology were examined in the mice.Meanwhile,the distribution of test articles in the blood was also measured.Results The two doses had no obvious effect on the injection site,body weight,food consumption,hematology,clinical chemistry of the serum and organ weight of the mice.The concentration of IFN-γ increased at the end of the recovery period in female mice at high doses.The histopathological changes associated with the test articles included aggregation of mixed cells in multiple organs and increased number of bone marrow cells in the sternum and thigh bones.In the blood,CD3~+,CD3~+CD4~+,and CD3~+CD8~+ cells were detected.The three kinds of cells showed consistent trends in a dose-dependent manner.On the 29th day after the last administration,the three kinds of cells were basically eliminated.Conclusion NOG mice show good tolerance to TIL after three administrations,and the three kinds of cells are basically eliminated in the blood at the end of the recovery.更多还原