Tumour growth inhibition in mice by glycosylated recombinant human lymphotoxin: analysis of tumour-regional mononuclear cells involved with its action.
We compared the antitumour effects of glycosylated LT (gLT), nonglycosylated LT and TNF against a solid tumour in mice. We found that: (a) The systemic administration of gLT showed significant antitumour activity. These effects were, however, quite small in nude mice. Nonglycosylated LT and TNF attained the same degree of effectiveness as gLT, but at a 5-times higher dose. The serum half-life of gLT was 3-fold longer than that of nonglycosylated LT and 22-fold longer than that of TNF. (b) The effect of gLT was significantly blocked by pretreatment with anti-asialo GM1 antibody. Treatment with gLT produced a significant reduction in numbers of tumour-regional mononuclear cells, which in turn, produced increases intensive necrosis. (c) Mononuclear cells in the tumour tissues before gLT-injection were predominantly IL-2 receptor +/CD3- cells and CD3+ cells. Pretreatment with the anti-asialo GM1 antibody produced a drastic reduction of IL-2 receptor +/CD3- cells. These findings suggest that the efficient antitumour effect of gLT is due to a longer serum half-life than that of nonglycosylated LT or TNF in vivo, and its function is largely mediated by IL-2 receptor +/CD3- cells.
Funahashi
I
I
Department of Pathology, Hyogo College of Medicine, Japan.
Watanabe
H
H
Abo
T
T
Indo
K
K
Miyaji
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000032:analysis; D016516:CD4-CD8 Ratio; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D006031:Glycosylation; D007109:Immunity / Q000187:drug effects; D007958:Leukocyte Count; D008233:Lymphotoxin-alpha / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008233:Lymphotoxin-alpha; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha