Combination Cancer Therapy Using an IL13-Targeted Toxin and a Vaccine
Posted Jul 25 2011 8:00pm
Description of Invention: Typical cancer treatments such as chemotherapy, radiation therapy and surgical resection are non-specific processes that kill healthy cells as well as diseased cells, ultimately resulting in discomfort and undesirable side-effects for patients. In an effort to reduce the burden on cancer patients, a tremendous effort has been placed on developing ways to increase the specificity of cancer treatments. One way to increase specificity is to identify proteins which are present on the surface of cancer cells but absent on normal healthy cells, and use that protein as a target for delivering a therapeutic agent. Because the therapeutic agent only reaches the diseased cell, patients are less likely to experience non-specific side-effects, reducing their pain burden during treatment.
IL13-receptor-alpha-2 (IL13-R-alpha-2) is a cell surface protein that is selectively expressed on certain diseased cells, including cancer cells. IL13-R-alpha-2 binds to the cytokine IL13, suggesting that a therapeutic agent fused to IL13 can target and kill only those cancer cells which express IL13-R-alpha-2. Our inventors previously constructed fusion proteins comprising (1) IL13 and (2) an active fragment of the bacterial toxin Pseudomonas exotoxin A (PE). These IL13-PE fusion proteins demonstrated the ability to selectively kill cancer cells that overexpressed IL13-R-alpha-2, as well as other types of diseased cells (asthma, pulmonary fibrosis) which overexpressed IL13-R-alpha-2. This suggested that IL13-PE fusion proteins were excellent candidates for new therapeutic agents.
The inventors recently sought methods to increase the effectiveness of these IL13-PE fusion proteins in the treatment of disease. This technology is directed to a combination therapy comprising (a) a DNA vaccine against IL13-R-alpha-2 and (b) an IL13-PE fusion protein. By combining these therapeutic approaches it is possible to kill certain cell types that express IL13-R-alpha-2 at high levels (such as cancer cells), making this combinatorial approach an attractive potential therapeutic.
Treatment of diseases associated with the increased expression of IL13-R-alpha-2.
Relevant diseases include pulmonary fibrosis, asthma and cancers such as pancreatic cancer, glioblastoma multiforme and other head and neck cancers.
The DNA vaccine only affects cells where IL13-R-alpha-2 expression is increased, limiting their effects to diseased cells.
IL13-PE fusion proteins also only kill cells that overexpress IL13-R-alpha-2, allowing specific targeting of treatment.
Targeted treatment decreases non-specific killing of healthy, essential cells, resulting in fewer side-effects and healthier patients.
Development Status: Preclinical stage of development.
For more information, see:
HHS Reference No. E-266-1994/0 — US Patents 5,614,191, 5,919,456 and 6,518,061
HHS Reference No. E-032-2000/0 — US Patent Publication US 20040136959 A1
HHS Reference No. E-296-2001/0 — US Patent 7,541,040
For Licensing Information Please Contact: David Lambertson Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: firstname.lastname@example.org Phone: 301-435-4632 Fax: 301-402-0220