Augmentation of Specific Tumor Killing Activity by Tumor-Infiltrating Lymphocytes (TIL) in the Presence of TNF-S AM2

The effect of TNF-S_AM2 on cytotoxic activity of tumor-infiltrating lymphocytes (TIL) was investigated. TIL were prepared from 11 human cancer patients. They were propagated by double in vitro stimulation with anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 weeks. The cytotoxic activity of TIL was tested with standard 4h ⁵¹Cr-release assays in the presence or the absence of TNF-S_AM2. In the presence of TNF-S_AM2 (500U/ml), the mean cytotoxic activity against autologous tumor cells was significantly augmented compared to that in its absence. However, the fact that cytotoxic activity against K562 and Daudi showed no difference whether substance was present or not, indicates that LAK and NK activity were not affected by TNF-S_AM2. Direct cytotoxicity by exogenously added TNF-S_AM2 to tumor cells was measured in 9 out of 11 cases and this revealed that cytotoxicity solely by TNF-S_AM2 was seen in 3 tumors. However, there was no correlation between the augmentation of cytotoxicity by TIL in the presence of TNF-S_AM2 and the cytotoxicity shown by TNF-S_AM2 alone. These results suggested that TIL therapy combined with administration of exogenous TNF may exert a synergistically stronger therapeutic effect on cancer.