Improved anti-tumor activity and safety of interleukin-13 receptor targeted cytotoxin by systemic continuous administration in head and neck cancer xenograft model.

Abstract

BACKGROUND:

IL-13 receptor (IL-13R) targeted cytotoxin, IL13-PE38QQR, has been shown to have very potent anti-tumor activity to IL-13R-expressing head and neck tumor cells in vitro and in vivo. However, its effect is limited in aggressive tumors. To further improve the anti-tumor activity and safety of IL-13 cytotoxin, we employed continuous infusion technique in animal model of head and neck cancer.

MATERIALS AND METHODS:

We surgically implanted continuous infusion (CI) pump intraperitoneally that released drug for 7 days, and its anti-tumor effect was evaluated. A comparison was made for antitumor activity and safety with intravenously (IV) administered IL-13 cytotoxin in a head and neck (KCCT873 and HN12) subcutaneous (SC) xenograft tumor models in nude mice. Vital organ toxicities were assessed by histologic examinations and blood serum chemistry analyses.

RESULTS:

The 50 or 75 micro g/kg/day for 7 days of IL-13 cytotoxin either by IV or CI administration did not show any difference in safety or anti-tumor activity. IV administration of 150 or 200 micro g/kg/day of IL-13 cytotoxin for 7 days was lethal to nude mice, whereas 200 micro g/kg/day X 7 days of CI administration was highly effective in the regression of established tumors without any toxicities. Additionally, CI administration of IL-13 cytotoxin (200 micro g/kg/day) showed growth inhibition of larger HN12 tumors in nude mice.

CONCLUSION:

With a CI schedule, IL-13 cytotoxin can be systemically administrated at approximately twice the dose otherwise given by daily IV bolus administration.

• Authors: Koji Kawakami, Syed R Husain, Mariko Kawakami, Raj K Puri
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) Vol. 8 Issue 8 Pg. 487-94 (Aug 2002) ISSN: 1076-1551 [Print] England
• PMID: 12435859 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Bacterial Toxins
• Exotoxins
• IL13RA1 protein, human
• Il13ra1 protein, mouse
• Interleukin-13
• Interleukin-13 Receptor alpha1 Subunit
• Receptors, Interleukin
• Receptors, Interleukin-13
• Virulence Factors
• ADP Ribose Transferases
• Pseudomonas aeruginosa exotoxin A

Topics

• ADP Ribose Transferases (administration & dosage, genetics, pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Bacterial Toxins (administration & dosage, genetics, pharmacology)
• Exotoxins (administration & dosage, genetics, pharmacology)
• Head and Neck Neoplasms (drug therapy, metabolism)
• Humans
• Infusions, Parenteral
• Injections, Intravenous
• Interleukin-13 (administration & dosage, pharmacology)
• Interleukin-13 Receptor alpha1 Subunit
• Mice
• Mice, Nude
• Mutation
• Receptors, Interleukin (drug effects)
• Receptors, Interleukin-13
• Transplantation, Heterologous
• Virulence Factors (administration & dosage, genetics, pharmacology)