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Chimeric Immunotoxins Targeting IL-13Rα2 Positive Human Cancers
FDA Technology Transfer
Antibody
Oncology
Target Identification or Validation
Summary
Many human cancers overexpress high affinity receptor for type 2 cytokine IL-13 called IL-13 receptor alpha 2 (IL-13Ralpha2) including head and neck cancer, prostate cancer, colorectal cancer, breast cancer, stomach cancers and cervical cancers. FDA inventors created recombinant chimeric protein fusions composed of an IL-13 targeting domain and a death inducing domain to specifically target and eliminate IL-13Ralpha2 positive human cancer cells. The targeting domain consists of either IL-13 or an antibody against IL-13Ralpha2. The other domain can be truncated Pseudomonas exotoxin (IL-13-PE), BCL2 associated agonist of cell death (IL13-BAD), or Fas-associated protein with death domain (IL13-FADD) that will kill the tumor cell.
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive solid cancer, with high mortality, and often painful due to perineural invasion (PNI) where cancer cells invade the surrounding nerves. PDAC commonly overexpresses IL-13Ralpha2 (greater than or equal to 75%), and the overexpression of IL-13Ralpha2 showed a correlation with worse pathologic grade and clinical stage of the disease. Thus, IL-13R targeted immunotoxins may not only inhibit primary tumor growth and metastasis but may also decrease PNI induced pain in patients with PDAC and other cancers.
Potential Commercial Applications
• Therapeutic for highly aggressive pancreatic ductal adenocarcinoma (PDAC)
• Personalized medicine for treating cancers overexpressing IL-13Ralpha2
Competitive Advantages
• Treats metastasis in addition to primary tumor
• As IL-13Ralphs2 overexpression is found in tumor cells undergoing perineural invasion the therapeutic alleviate the associated pain
• Toshio Fujisawa, Takeshi Shimamura
• Tatiana Paula T Ferreira, Ana Carolina S de Arantes
PCT-US2022-030011 (2022.05.19)
• "A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma". Toshio Fujisawa et al. Cancers (Basel). 2020 May; 12(5): 1294
• "IL-13 immunotoxin accelerates resolution of lung pathological changes triggered by silica particles in mice". Tatiana Paula T Ferreira et al. J Immunol. 2013 Nov 15;191(10):5220-9
