About TCRT

TCRT has been on continuous publication since 2002. It is covered currently by all the major data systems such as Medline, PubMed, Web of Science, Thomson's ISI and SCI and Scopus.

The 2012 Impact factor for TCRT is 1.943

TCRT Open Access
TCRT seeks original articles
Cancer Watch

Convection-enhanced Delivery of Interleukin-13 Receptor-directed Cytotoxin for Malignant Glioma Therapy* (p. 239-250)

The treatment of patients with malignant brain tumors, in particular glioblastoma multiforme (GBM) is very challenging because of their diffuse infiltrative nature and the cytological heterogeneity. The median survival of patients with newly diagnosed GBM is only 12-15 months, and only 8-12% of them survive for two years. Novel approaches for brain tumor therapy are needed. Recently, targeted therapies have emerged as promising modality for cancer targeting. We have discovered that high affinity plasma membrane receptor for interleukin-13 (IL-13), an immune regulatory cytokine, is over-expressed in 60-80% of malignant brain tumors. To target these IL-13R, we generated a chimeric fusion protein, composed of human IL-13 and mutated Pseudomonas exotoxin (PE), termed IL-13 cytotoxin (IL13-PE), and tested its cytotoxicity to IL-13R-expressing GBM cells. IL-13 cytotoxin was highly potent and selective in killing IL-13R-expressing GBM cells. In contrast, normal cells including brain, immune, and endothelial cells were generally not affected by this cytotoxin due to no or low expression of IL-13R. In vivo pre-clinical studies for safety and toxicity were also performed in mice, rats, and monkeys, and IL-13 cytotoxin was found to be well tolerated by both systemic and intracerebral administrations. IL-13 cytotoxin was found to mediate remarkable efficacy in animal models of human brain tumors. Encouraged by these pre-clinical studies, four Phase 1/2 clinical trials in adult patients with recurrent malignant glioma have been completed. These clinical trials involved convection-enhanced delivery (CED) of IL-13 cytotoxin either intratumoral or intraparenchymal after resection of tumor. CED is a novel loco-regional drug delivery method for intracranial tumors that relies on a continuous pressure gradient to distribute drug into interstitial space. This route of IL-13 cytotoxin administration appears to be very well tolerated and have a good risk-benefit profile. Most recently, a randomized controlled Phase 3 clinical trial (PRECISE) with intraparenchymal IL-13 cytotoxin administration was completed and subjects are being monitored for safety and survival.

Key words: Interleukin-13; IL-13 receptor; Immunotoxin; Cytotoxin; Glioblastoma multiforme; Convection-enhanced delivery; Targeted brain tumor therapy.

*The views presented in this article do not necessarily reflect those of the Food and Drug Administration.




Purchase Downloadable Full-text PDF of Articles

Corporate User

$100.00

University/Academic User

$50.00

TCRT June 2006

category image
Volume 5
No. 3 (p 183-298)
June 2006
ISSN 1533-0338

Mitomu Kioi, D.D.S. Ph.D.1
Syed R. Husain, Ph.D.1
David Croteau, M.D.2
Sandeep Kunwar, M.D.3
Raj K. Puri, M.D. Ph.D.1,*

1Tumor Vaccines and Biotechnology Branch
Division of Cellular and Gene Therapies
Center for Biologics Evaluation and Research
Food and Drug Administration
29 Lincoln Drive MSC 4555
Bethesda, MD 20892, USA
2NeoPharm Inc.
Lake Forest, IL
3University of California in San Francisco
San Francisco, CA, USA
*raj.puri@fda.hhs.gov