PHARMACODYNAMICS OF RECOMBINANT IFN-BETA DURING LONG-TERM TREATMENT OF MALIGNANT-MELANOMA

The pharmacodynamics and biologic activities of recombinant human inte rferon-beta (rHuIFN-beta) derived from chinese hamster ovary (CHO) cel ls were examined during long-term therapy in 7 melanoma patients. The CHO-derived rHuIFN-beta was given s.c. in a dose of 3 x 10(6) U three times per week for 24 weeks, Serum levels of IFN could not be detected before and 48 h after the s.c. injections. 2'-5'-Oligoadenylate synth etase (2-5 GAS), beta(2)-microglobulin, and neopterin levels increased significantly 48 h after application, with a maximum after 96 h, Subs equently, the values decreased and remained only slightly elevated dur ing the long-term therapy, Natural killer (NK) cell activity increased in the first 96 h significantly and fell below pretreatment values af ter 4 weeks, The decrease of biologic response could not be attributed to the occurrence of anti-IFN-beta antibodies because only 2 of the 7 patients developed neutralizing antibodies after 16 and 24 weeks of t reatment, respectively, This trial confirms the biologic potency of CH O-derived rHuIFN-beta. However, the selected parameters demonstrate th at immunostimulation is only possible over a short treatment period.