Antitumor effects of novel immunoactive peptides, FK-156 and its synthetic derivatives.
Effects produced by intratumor or systemic application of FK-156 and its synthetic derivatives on the syngeneic P388-DBA/2 mouse system were investigated. Among 21 compounds tested, FK-156, FK-565, FR-46758, FR-48217, FR-46091 and FR-47920 substantially suppressed tumor growth when directly injected into a tumor mass and further experiments showed that FK-156, FK-565 and FR-46758 were effective even when administered subcutaneously into site remote from tumor. The mechanisms of growth inhibition are strongly suggested to be host mediated, because these three compounds have remarkably low cytotoxicity against P388 cells in vitro. A single dose of FK-565, however, markedly decreased body weight in healthy DBA/2 mice, whereas FK-156 and FR-46758 did not. These results indicate the superiority of FK-156 and FR-46758 as immunotherapeutic agents over FK-565 with respect to their safety for treatment of cancer. Although significant life-span prolongation could not be seen in the two-injection regimen of six compounds in either system, systemic multiple injections of FK-156 and FR-46758 provided a statistically significant increase in the median survival time of P388 tumor bearing mice.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000599:Amino Acids, Diamino / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003960:Diaminopimelic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D007372:Interferons / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D000599:Amino Acids, Diamino; D000970:Antineoplastic Agents; D003960:Diaminopimelic Acid; C034330:FK 156; D007372:Interferons