POSSIBLE BIOLOGICAL INDICATORS OF THE RESPONSE TO RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA IN PATIENTS WITH ADVANCED NEOPLASMS

Tumour Necrosis Factor alpha (TNF alpha) immunotherapy, in addition to that of Interleukin-2 immunotherapy, represents one of the most promi sing biotherapies for human neoplasms. In order to identify immunologi cal parameters of prognostic value we studied changes in immune respon se during first cycle of treatment with hree TNF alpha.The study inclu ded 21 locally advanced or metastatic solid tumor patients (M/F:12/9 m edian age: 57 years, range 38-65) for whom no other standard therapy w as available. TNF alpha was administered before midday by a 20-minute intravenous infusion at a dose of 75 mu g/day for 5 consecutive days c orresponding to one cycle. In the absence of progression two further c ycles of TNF alpha were given at 14 day intervals during which the dos e was increased by 50 mu g/day i.e. 2nd cycle- 100 mu g/day, 3rd cycle - 150 mu g/day. Of 21 patients evaluated for both clinical and immunol ogical responses, 4 had complete response and 4 patients had partial r esponse. The present study suggests that TNF alpha biotherpay is not a ssociated with an increase in the number of circulating lymphocytes. R egarding lymphocyte subtype, a slight increase has been observed as fa r as T lymphocyte subsets are concerned. The CD4/CD8 ratio in cancer p atients treated with hree TNF alpha showed significantly lower values than before treatment. On the basis of in vitro experiments an increas e in NK cell activation in tissue culture, in addition to an increase of LAK cells, was observed.