Differences in the bioactivity of recombinant human TNF, LT, and T-cell-derived LT-3 on transformed cells in vitro and the Meth A tumor growing in BALB/c mice.
Cytolytic human T cells and the continuous human T cell line YM 1.2 can secrete a lymphotoxin (LT) form, termed LT-3, when stimulated in vitro. LT-3 is immunologically related to, but functionally distinct from, both alpha LT and tumor necrosis factor (TNF). Purified, native LT-3 and recombinant human LT and TNF were tested for their ability to destroy a panel of primary and continuous cell lines in vitro and cause necrosis of 8- to 9-day cutaneous Meth A tumors growing in BALB/c mice. LT-3 is more effective than either LT or TNF in inducing destruction of continuous cell lines in vitro. LT-3 induces destruction of cell lines that are resistant to both TNF and LT, and much less LT-3 is required to destroy cells that are LT and/or TNF sensitive. In contrast, none of these mediators had any measurable negative effects when tested on primary human fibroblasts. Additional studies revealed that LT-3 is also active in vivo and can cause necrosis of cutaneous Meth A tumors when administered intraperitoneally or intratumorally on BALB/c mice. LT-3 induces more rapid, consistent, and complete tumor necrosis than equivalent doses of either LT or TNF.
Granger
G A
GA
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Masunaka
I
I
Averbook
B
B
Kobayashi
M
M
Fitzgerald
M
M
Yamamoto
R
R
D000818:Animals; D002461:Cell Line, Transformed; D006801:Humans; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha