Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer.

Abstract

Although interleukin-13 receptors (IL-13R) are overexpressed on several head and neck cancer cell lines, a majority of cell lines express only low levels of IL-13R. We have found that the primary interleukin-13-binding protein IL-13Ralpha2 chain plays an important role in ligand binding and internalization. We showed that the gene transfer of IL-13Ralpha2 chain into various solid tumor cell lines that express few IL-13Rs can dramatically sensitize cells to the cytotoxic effect of a recombinant chimeric protein composed of interleukin-13 and a mutated form of Pseudomonas exotoxin A, IL13-PE38QQR. Based on the expression of IL-13R, we have classified five head and neck cancer cell lines into two groups: (a) IL-13Ralpha2 chain-positive cell lines (SCC-25 and KCCT873); and (b) IL-13Ralpha2 chain-negative cell lines (A253, YCUT891, and KCCT871). By plasmid-mediated stable gene transfer, we demonstrate that not only IL-13Ralpha2 chain-positive head and neck cancer cell lines but also IL-13Ralpha2 chain-negative cell lines can dramatically increase sensitivity to IL-13 toxin by 520-1000-fold compared with mock-transfected control cells after genetic alteration to express high levels of the IL-13Ralpha2 chain. In animal studies, i.p. or intratumoral administration of IL13-PE38QQR given daily or on alternate days for 3-5 days showed dramatic tumor response with complete remission in intratumorally injected tumors in both IL-13Ralpha2 chain-positive and -negative but transfected with IL-13Ralpha2 chain head and neck tumor implanted s.c. in nude mice. These results demonstrate that by using a combination approach of gene transfer and systemic or locoregional cytotoxin therapy, the IL-13R represents a new potent target for head and neck cancer therapy.

• Authors: K Kawakami, M Kawakami, B H Joshi, R K Puri
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 16 Pg. 6194-200 (Aug 15 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11507072 (Publication Type: Journal Article)

Chemical References

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

Topics

• ADP Ribose Transferases
• Animals
• Bacterial Toxins
• Carcinoma, Squamous Cell (drug therapy, genetics, metabolism)
• Exotoxins (administration & dosage, metabolism, pharmacology)
• Head and Neck Neoplasms (drug therapy, genetics, metabolism)
• Humans
• Interleukin-13 (administration & dosage, metabolism, pharmacology)
• Interleukin-13 Receptor alpha1 Subunit
• Mice
• Mice, Nude
• Receptors, Interleukin (genetics, metabolism)
• Receptors, Interleukin-13
• Recombinant Fusion Proteins (administration & dosage, metabolism, pharmacology)
• Transfection
• Tumor Cells, Cultured
• Virulence Factors
• Xenograft Model Antitumor Assays