Antitumor effect of recombinant human tumor necrosis factor-alpha analog combined with desmuramyl dipeptides LK-409 or LK-410 on sarcoma in mice.
Antitumor effect of recombinant human tumor necrosis factor (TNF)-alpha lacking one to three amino acids from the N terminal part (TNFNv3) was tested for its antitumor effect on subcutaneous fibrosarcoma SA-1 tumors. Peritumoral treatment with 5 x 10(4) U TNFNv3 three times every second day significantly delayed tumor growth. Treatment with 10 times higher dose (5 x 10(5) U) produced 6.0 +/- 1.0 days tumor growth delay, but had side effects such as weight loss. The two new desmuramyl N-acyl dipeptides, LK-409 and LK-410, also exhibited such effect; however, the tumor growth delay was barely significant. The treatment was performed with two concentrations (2.5 micrograms and 25.0 micrograms) applied intraperitoneally for 5 consecutive days, without a dose-dependent effect. Combined treatment with TNFNv3 and desmuramyl dipeptides augmented the antitumor effect of treatments. The effect was additive and significant in the combination of 2.5 micrograms LK-410 with 5 x 10(5) U TNFNv3. LK-410 treatment also reduced the side effects of TNFNv3. The results indicate that combined treatment with both biological response modifiers is effective in tumor treatment.
Sersa
G
G
Department of Tumor Biology and Biotherapy, Institute of Oncology, Ljubljana, Slovenia.
Novakovic
S
S
Stalc
A
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004151:Dipeptides; C079179:LK 409; C079180:LK 410; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine