Recombinant human tumor necrosis factor mediates regression of a murine sarcoma in vivo via Lyt-2+ cells.
The role of an immune response in recombinant-human-tumor-necrosis-factor(rHTNF)-mediated regression of a weakly immunogenic, MCA-106 sarcoma in vivo was examined. C57BL/6 mice bearing established 10-day s.c. tumor were treated with single i.v. doses (8 micrograms) of rHTNF. rHTNF administration resulted in marked hemorrhagic necrosis and subsequent regression of tumor in treated mice. Mice cured of MCA-106 sarcoma by rHTNF specifically rejected a subsequent challenge (5 x 10(5) cells) of the same tumor (P less than 0.01) but not of the antigenically distinct, syngeneic MCA-105 sarcoma. Tumor bearers were depleted in vivo of selective T-cell subsets by the systemic administration of specific monoclonal antibodies before rHTNF therapy. rHTNF-induced regression, but not hemorrhagic necrosis of the MCA-106 sarcoma was blocked in mice depleted of Lyt-2+ cells, but not of L3T4+ cells. The in vivo role of T-cell subsets in rHTNF-mediated tumor regression is discussed.
Surgery Branch, National Cancer Institute, Bethesda, MD 20892.
A L
AL
Asher
J J
JJ
Mulé
S A
SA
Rosenberg
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000950:Antigens, Ly / Q000276:immunology*; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D013154:Spleen; D013601:T-Lymphocytes / Q000145:classification* / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha