Interleukin 13

Our Critical Discovery

Interleukin 13 is a naturally occurring compound in the body that plays a role in the function of the immune system. The IL-13 receptor is found in most normal organs. In 1995, Dr. Waldemar Debinski, Targepeutics’ Founder and Consulting Scientific Officer, discovered that high-grade astrocytomas, the most prevalent and the deadliest form of brain cancer, over-express IL-13 receptors in numbers significantly higher than normal tissue. Additionally, Dr. Debinski discovered that high-grade astrocytomas, including glioblastoma multiforme, express a different, more restrictive IL-13 receptor.


Approach: Specific Targeting

These discoveries led Dr. Debinski to develop mutated IL-13 based compounds that bind IL-13 receptors present in high-grade astrocytomas more tightly than normal tissue IL-13 receptors. Moreover, Targepeutics’ advanced compounds do not bind normal cell receptors with much less affinity, directed towards the more restrictive IL-13 receptors expressed on cancer cells. The specificity of the mutated IL-13 molecules makes them ideal candidates for drugs as well as imaging and diagnostic applications for the management of brain, pancreas, head and neck, and skin cancers.


Applications: Brain Cancer Treatment

The first application of this platform is to combine the targeting molecule, a rationally mutated IL-13, with a cellular toxin. This compound acts as a “smart bomb”, delivering the cytotoxin that is specific to cancer cells by local administration through a tiny catheter. Targepeutics’ second generation IL-13 cytotoxin and lead compound is GB-13. Other combinations of less specific targeting molecules and toxins developed by other companies have already gone into clinical trials with the FDA’s approval, achieving Fast Track designation. Targepeutics will file for both Fast Track and Orphan Drug status concomitantly with its Investigational New Drug Application. 

 

Anti-tumor effect of an IL-13-based cytotoxin on human glioma xenografts in mice. Treatments were started when established tumors were formed.

Brain Cancer Imaging and/or Diagnostic Imaging

A second application in this platform is to attach a radioisotope suitable for medical imaging to the target molecule (Glio-Image). This compound will be useful in the imaging or diagnostic imaging of high-grade astrocytomas. A prototype compound has been produced and preliminarily successfully tested in the lab of Dr. Debinski. This imaging compound would not only be important for the 40,000 annual diagnostic tests for brain cancer in the U.S. alone but also as a monthly and then biannual follow-up test after treatment by GB-13 or next generation compound for the over 8,000 newly diagnosed patients yearly. This radioactive compound also shows promise as a therapeutic agent as well, being able to deliver cytotoxic radiation energy in a much more specific and localized manner than conventional radiation therapy.

Delivery of a cytotoxic agent specifically to tumor cells while sparing normal cells is a realistic goal if the tumor cells express a cell surface molecule that is not present in normal cells or is expressed in much lower amounts. This has been discovered to be the case, and Targepeutics’ technology takes full advantage of these differences.
Brain Cancer Diagnostics

A third application would be a diagnostic kit for brain tumor tissue. A quick assessment of Targepeutics’ compound binding could determine if over-expression of IL-13 is present, marking a high-grade astrocytoma.

 

IL-4 and IL-13 compete for a shared binding site on normal cells. The shared receptor consists of two subunits, which bind either cytokine with high affinity when they are associated as a heterodimer. On human glioma cells and some other solid tumor cells, studies identified a different form of receptor that binds IL-13 but not IL-4.
Brain Cancer Chemotherapeutic Treatment

A fourth application would be attaching a targeting molecule to a conventional chemotherapeutic or another small molecule with anti-tumor properties. This application yields specific and targeted chemotherapeutics that would have potentially better tumor penetration and a much lesser toxicity.  This is an attractive delivery method with a chemotherapeutic agent on the market for a specific indication, potentiall producing synergistic effects with increased patent life.

Head and Neck, and Skin Cancer Applications

Studies have shown that head and neck carcinoma, and AIDS-related Kaposi’s sarcoma over-express the more restrictive IL-13 receptor. At least 4 Targepeutics compounds will be targeted for clinical trials in these cancers.Targepeutics has entered into a joint research agreement with a Fortune 500 major pharmaceutical company to explore these and other cancer applications for this platform. We are excited that the participation of this company validates the promise of the technology.

Most of today’s cancer therapies kill tumor cells, but also kill normal cells. We believe we have found a targeted way to attack just tumor cells. GB-13 begins this new direction. Waldemar Debinski, M.D., Ph.D. Founder