Antitumor effect of recombinant human tumor necrosis factor-alpha analog combined with desmuramyl dipeptides LK-409 or LK-410 on sarcoma in mice

• Published in: Molecular biotherapy Vol. 4; no. 4; p. 188
• Main Authors: Sersa, G, Novakovic, S, Stalc, A
• Format: Journal Article
• Language: English
• Published: United States 01-12-1992
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - analogs & derivatives; Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Animals; Antineoplastic Agents - pharmacology; Dipeptides - pharmacology; Humans; Mice; Peptide Fragments - pharmacology; Recombinant Proteins - pharmacology; Sarcoma, Experimental - drug therapy; Tumor Necrosis Factor-alpha - chemistry; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0952-8172

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.