S. Goto et al., AUGMENTATION OF SPECIFIC TUMOR KILLING ACTIVITY BY TUMOR-INFILTRATINGLYMPHOCYTES (TIL) IN THE PRESENCE OF TNF-S-AM2, Cancer biotherapy, 10(1), 1995, pp. 37-44
The effect of TNF-S-AM2 on cytotoxic activity of tumor-infiltrating ly
mphocytes (TIL) was investigated. TIL were prepared from 11 human canc
er patients. They were propagated by double in vitro stimulation with
anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 wee
ks. The cytotoxic activity of TIL was tested with standard 4h Cr-51-re
lease assays in the presence or the absence of TNF-S-AM2. In the prese
nce of TNF-S-AM2 (500U/ml), the mean cytotoxic activity against autolo
gous tumor cells was significantly augmented compared to that in its a
bsence. However, the fact that cytotoxic activity against K562 and Dau
di showed no difference whether substance was present or not, indicate
s that LAK and NK activity were not affected by TNF-S-AM2. Direct cyto
toxicity by exogenously added TNF-S-AM2 to tumor cells was measured in
9 out ofll cases and this revealed that cytotoxicity solely by TNF-S-
AM2 was seen in 3 tumors. However, there was no correlation between th
e augmentation of cytotoxicity by TIL in the presence of TNF-S-AM2 and
the cytotoxicity shown by TNF-S-AM2 alone. These results suggested th
at TIL therapy combined with administration of exogenous TNF may exert
a synergistically stronger therapeutic effect on cancer.