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Immunological Mornitoring After TIL Treatment of Advanced Human Malignancy
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Abstract:
Tumor infiltrating lymphocytes(TILs) were isolated by enzymatic digestion and discontinuous gradient centrifugation from 8 human advanced tumors (4 stomach carcinoma, 2 liver cancer, 1 non-small-cell lung carcinoma and 1 colon cancer). These cells were cultured in complete RPMI 1640 medium supplemented with l000U/ml of rhIL2 for 4-6 weeks, till the cell number reach over l09/total, reinfused to the same patients i.v. meanwhile, the patients received 105U of rhIL2 i.m for 5 days. One week before and one month after TIL infusion periphery blood from the patients was collected and the mononuclear cells were isolated. Cytotoxicity against a panel of tumor cell targets by MTT colorometric assay and lymphocyte phenotype by two-color flow cytometry were mornitored. The results showed that there was significant increase in the killing ability to the tested tumor targets to different extent, especially the killing to the target cells which shared the same histological type with the patients tumor. (43 against 1249 lytic units p<0.05), an enhancement of fluoreceint intensity on CD4 and CD8 cell subsets. ( T4 1.92 to 3.98,4.45 to 7.2 p<0.05) All the findings indicate that TILs plus lower dose rhIL2 are able to up-regulate the cellular immunological state in patients through immunological regulatory effect by cytokine cascade addition to the direct cytotoxicity.
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