Pharmacodynamics of recombinant IFN-beta during long-term treatment of malignant melanoma.
The pharmacodynamics and biologic activities of recombinant human interferon-beta (rHuIFN-beta) derived from chinese hamster ovary (CHO) cells 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 synthetase (2-5 OAS), beta 2-microglobulin, and neopterin levels increased significantly 48 h after application, with a maximum after 96 h. Subsequently, the values decreased and remained only slightly elevated during the long-term therapy. Natural killer (NK) cell activity increased in the first 96 h significantly and fell below pretreatment values after 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 treatment, respectively. This trial confirms the biologic potency of CHO-derived rHuIFN-beta. However, the selected parameters demonstrate that immunostimulation is only possible over a short treatment period.
University of Tuebingen, Department of Dermatology, Germany.
G
G
Fierlbeck
A
A
Ulmer
T
T
Schreiner
W
W
Stroebel
U
U
Schiebel
J
J
Brzoska
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D016466:CHO Cells; D006224:Cricetinae; D004334:Drug Administration Schedule; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000097:blood / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D019798:Neopterin; D011994:Recombinant Proteins / Q000097:blood / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000378:metabolism*
D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase