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 FG...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1992-01, Vol.52 (1), p.227-230
Main Authors: Beitz, J G, Davol, P, Clark, J W, Kato, J, Medina, M, Frackelton, Jr, A R, Lappi, D A, Baird, A, Calabresi, P
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Phytogenic - adverse effects
Antineoplastic Agents, Phytogenic - pharmacology
Dose-Response Relationship, Drug
Drug Combinations
Drug Screening Assays, Antitumor
Female
Fibroblast Growth Factor 2 - adverse effects
Fibroblast Growth Factor 2 - metabolism
Fibroblast Growth Factor 2 - pharmacology
Humans
Immunotoxins
Male
Melanoma - drug therapy
Mice
Mice, Nude
N-Glycosyl Hydrolases
Neuroblastoma - drug therapy
Ovarian Neoplasms - drug therapy
Pilot Projects
Plant Proteins - adverse effects
Plant Proteins - pharmacology
Receptors, Cell Surface - metabolism
Receptors, Fibroblast Growth Factor
Ribosome Inactivating Proteins, Type 1
Teratoma - drug therapy
Tumor Cells, Cultured - drug effects
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Summary: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.
ISSN:0008-5472