Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo.
Many cancer cell lines express basic fibroblast growth factor (FGF) receptors, making them potential targets for the delivery of FGF-based cytotoxic compounds. To this end, we have investigated the antitumor activity of a novel mitotoxin, Fibroblast Growth Factor-saporin (FGF-SAP), a conjugate of FGF and the ribosome-inactivating protein, saporin. In vitro, FGF-SAP is cytotoxic for human melanoma, teratocarcinoma, and neuroblastoma cells expressing FGF-receptors. Mice treated with FGF-SAP i.v., on a variety of schedules, showed dramatic tumor growth inhibition with minimal toxicity. Thus, FGF-SAP appears to be a well-tolerated and potent antitumor agent. The potential of FGF-targeted cytotoxicity is discussed.
Beitz
J G
JG
Roger Williams Cancer Center, Brown University, Providence, Rhode Island 02908.
Davol
P
P
Clark
J W
JW
Kato
J
J
Medina
M
M
Frackelton
A R
AR
Lappi
D A
DA
Baird
A
A
Calabresi
P
P
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009699:N-Glycosyl Hydrolases; D009447:Neuroblastoma / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D010940:Plant Proteins / Q000009:adverse effects / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013724:Teratoma / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D000922:Immunotoxins; D010940:Plant Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins