Activation of tumoricidal properties in macrophages and inhibition of experimentally-induced murine metastases by a new synthetic acyltripeptide, FK-565.
The effect of FK-565, a novel low molecular weight (MW) acyltripeptide, on tumoricidal properties of murine macrophages is reported here. Peritoneal macrophages (PMs) harvested from C57BL/6 mice and beige mice were rendered cytotoxic to syngeneic B16 melanoma cells following their interaction in vitro with FK-565. Maximal and reproducible activation of tumoricidal properties in PM were obtained by interaction in vitro with 25 micrograms/ml of FK-565 for a 24 h period, and as little as 0.5 microgram/ml of FK-565 was sufficient to induce significant cytotoxicity. Murine PMs activated by FK-565 in vitro were cytotoxic to syngeneic and xenogeneic tumor cells, but did not affect allogeneic nontumor cells. The PMs were also activated to kill B16 melanoma cells by intraperitoneal injections of FK-565 (10 mg/kg). Multiple injections of FK-565 into mice also slightly but significantly inhibited lung metastases. These results suggest that FK-565 has potential as an effective immunopotentiator in immunotherapy.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000599:Amino Acids, Diamino / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005260:Female; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides
D000276:Adjuvants, Immunologic; D000599:Amino Acids, Diamino; D009842:Oligopeptides; D003960:Diaminopimelic Acid; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine