Toxicity study of tumor infiltrating lymphocytes in mice with severe immunodeficiency
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-y 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.