Experimental local therapy of human melanoma with lytic magainin peptides.
Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells. Here we demonstrate in vitro that MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin analogue) were more lytic for 17 human melanomas than for normal melanocytes. Melanomas established s.c. in athymic nude mice and then injected once with the peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect. Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI-511. Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long-term damage to normal tissues.
Soballe
P W
PW
Wistar Institute, Philadelphia, PA 19104.
Maloy
W L
WL
Myrga
M L
ML
Jacob
L S
LS
Herlyn
M
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects; D016038:Skin Transplantation; D014407:Tumor Cells, Cultured
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C091558:MSI 511; D010455:Peptides