Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients
- Univ. of California, Irvine (United States)
- Genetech Inc., San Francisco, CA (United States)
- John Kennedy Cancer Center, Indio, CA (United States)
- Children's Hospital, Los Angeles, CA (United States)
- Memorial Cancer Inst., Long Beach, CA (United States)
- Univ. of California, Irvine (United States) Memorial Cancer Inst., Long Beach, CA (United States)
Serum ultrafiltrates (SUF) from human patients with different types of cancer contain a blocking factor (BF) that inhibits the cytolytic activity of human tumor necrosis factor {alpha} (TNF-{alpha}) in vitro. BF is a protein with a molecular mass of 28kDa on reducing sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE). The active material was purified to homogeneity by a combination of affinity chromatography, PAGE, and high-pressure liquid chromatography. Amino acid sequence analysis revealed that BF is derived from the membrane TNF receptor. Purified BF blocks the lytic activity of recombinant human and mouse TNF-{alpha} and recombinant human lymphotoxin activity of TNF-{alpha} and recombinant human lymphotoxin on murine L929 cells in vitro. However, BF inhibits the lytic activity of TNF-{alpha} more effectively than it does that of lymphotoxin. The BF also inhibits the necrotizing activity of recombinant human TNF-{alpha} when coinjected into established cutaneous Meth A tumors in BALB/c mice. The BF may have an important role in (i) the regulation and control of TNF-{alpha} and lymphotoxin activity in cancer patients, (ii) interaction between the tumor and the host antitumor mechanisms, and (iii) use of systemically administered TNF-{alpha} in clinical trials with human cancer patients.
- OSTI ID:
- 5822267
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:22; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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