| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration [S. R. H., N. B., R. K. P.], and Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute [R. J. K., I. P.], National Institutes of Health, Bethesda, Maryland 20892
No curative therapy is available for malignant gliomas. We have discovered that human glioblastoma cells express high affinity interleukin-4 receptor (IL-4R), which is an attractive target for receptor-directed IL-4 toxin therapy. The IL-4 toxin, IL-4(38-37)-PE38KDEL, is a fusion protein containing translocation and enzymatic domains of Pseudomonas exotoxin and a circularly permuted human IL-4. The IL-4 toxin binds specifically to the IL-4R and is highly cytotoxic to glioblastoma cells, as determined by clonogenic and protein synthesis inhibition assays. Intratumoral administration of the IL-4 toxin given on alternate days for 3–4 doses into U251 glioblastoma flank tumors in nude mice, showed a complete remission of small (
13 mm3) and large (60 mm3) tumors in all animals, without any evidence of toxicity. A significant antitumor activity was also observed when the IL-4 toxin was administered via i.p. and i.v. routes. These results demonstrate that the IL-4 toxin may be a new therapeutic drug for the treatment of human glioblastoma. Therefore, we have begun a Phase I clinical trial with IL-4(38-37)-PE38KDEL for treatment of human glioblastoma.
1 To whom requests for reprints should be addressed, at Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, NIH, Building 29B, Room 2NN10, 29 Lincoln Drive MSC 4555, Bethesda, MD 20892. Phone: (301) 827-0471; Fax: (301) 827-0449; E-mail: Puri@A1.CBER.FDA.GOV.
Received 1/26/98. Accepted 6/10/98.
This article has been cited by other articles:
|
|
 |
|
  B. D. Beseth, R. B. Cameron, P. Leland, L. You, F. Varricchio, R. J. Kreitman, R. A. Maki, D. M. Jablons, S. R. Husain, and R. K. Puri Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts Ann. Thorac. Surg., August 1, 2004; 78(2): 436 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. de Jong, G. L. Scheffer, H. J. Broxterman, J. H. Hooijberg, J. W. Slootstra, R. H. Meloen, R. J. Kreitman, S. R. Husain, B. H. Joshi, R. K. Puri, et al. Multidrug-Resistant Tumor Cells Remain Sensitive to a Recombinant Interleukin-4-Pseudomonas Exotoxin, Except When Overexpressing the Multidrug Resistance Protein MRP1 Clin. Cancer Res., October 15, 2003; 9(13): 5009 - 5017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawakami, M. Kawakami, S. R. Husain, and R. K. Puri Effect of Interleukin (IL)-4 Cytotoxin on Breast Tumor Growth after in Vivo Gene Transfer of IL-4 Receptor {alpha} Chain Clin. Cancer Res., May 1, 2003; 9(5): 1826 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Husain, K. Kawakami, M. Kawakami, and R. K. Puri Interleukin-4 Receptor-targeted Cytotoxin Therapy of Androgen-dependent and -independent Prostate Carcinoma in Xenograft Models Mol. Cancer Ther., March 1, 2003; 2(3): 245 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kawakami, K. Kawakami, V. A. Stepensky, R. A. Maki, H. Robin, W. Muller, S. R. Husain, and R. K. Puri Interleukin 4 Receptor on Human Lung Cancer: A Molecular Target for Cytotoxin Therapy Clin. Cancer Res., November 1, 2002; 8(11): 3503 - 3511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, W. A. Hall, N. Jin, D. A. Todhunter, A. Panoskaltsis-Mortari, and D. A. Vallera Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein in vitro and in vivo in nude mice Protein Eng. Des. Sel., May 1, 2002; 15(5): 419 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ichinose, X.-H. Liu, N. Hagihara, and R. J. Youle Extracellular Bad Fused to Toxin Transport Domains Induces Apoptosis Cancer Res., March 1, 2002; 62(5): 1433 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawakami, M. Kawakami, P. Leland, and R. K. Puri Internalization Property of Interleukin-4 Receptor {alpha} Chain Increases Cytotoxic Effect of Interleukin-4 Receptor-targeted Cytotoxin in Cancer Cells Clin. Cancer Res., January 1, 2002; 8(1): 258 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Strome, K. Kawakami, D. Alejandro, S. Voss, J. L. Kasperbauer, D. Salomao, L. Chen, R. A. Maki, and R. K. Puri Interleukin 4 Receptor-directed Cytotoxin Therapy for Human Head and Neck Squamous Cell Carcinoma in Animal Models Clin. Cancer Res., January 1, 2002; 8(1): 281 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Joshi, P. Leland, A. Asher, R. A. Prayson, F. Varricchio, and R. K. Puri In Situ Expression of Interleukin-4 (IL-4) Receptors in Human Brain Tumors and Cytotoxicity of a Recombinant IL-4 Cytotoxin in Primary Glioblastoma Cell Cultures Cancer Res., November 1, 2001; 61(22): 8058 - 8061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kobayashi, J. A. Carrasquillo, C. H. Paik, T. A. Waldmann, and Y. Tagaya Differences of Biodistribution, Pharmacokinetics, and Tumor Targeting between Interleukins 2 and 15 Cancer Res., July 1, 2000; 60(13): 3577 - 3583. [Abstract] [Full Text]
|
|
|
|
|
|
K. Kawakami, P. Leland, and R. K. Puri Structure, Function, and Targeting of Interleukin 4 Receptors on Human Head and Neck Cancer Cells Cancer Res., June 1, 2000; 60(11): 2981 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Rand, R. J. Kreitman, N. Patronas, F. Varricchio, I. Pastan, and R. K. Puri Intratumoral Administration of Recombinant Circularly Permuted Interleukin-4-Pseudomonas Exotoxin in Patients with High-Grade Glioma Clin. Cancer Res., June 1, 2000; 6(6): 2157 - 2165. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. R. Husain and R. K. Puri Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft Blood, June 1, 2000; 95(11): 3506 - 3513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rajagopal and R. J. Kreitman Recombinant Toxins That Bind to the Urokinase Receptor Are Cytotoxic without Requiring Binding to the alpha 2-Macroglobulin Receptor J. Biol. Chem., March 10, 2000; 275(11): 7566 - 7573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Frankel, R. J. Kreitman, and E. A. Sausville Targeted Toxins Clin. Cancer Res., February 1, 2000; 6(2): 326 - 334. [Abstract] [Full Text]
|
|
|
|
|
|
H. Kiaris, A. V. Schally, A. Nagy, B. Sun, K. Szepeshazi, and G. Halmos Regression of U-87 MG Human Glioblastomas in Nude Mice after Treatment with a Cytotoxic Somatostatin Analog AN-238 Clin. Cancer Res., February 1, 2000; 6(2): 709 - 717. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. K. Puri Toxicologic Pathology of Cytokines, Cytokine Receptors, and Other Recombinant Human Proteins: Development of a Recombinant Interleukin-4-Pseudomonas Exotoxin for Therapy of Glioblastoma Toxicol Pathol, January 1, 1999; 27(1): 53 - 57. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
