Therapeutic Immunotoxins with Increased Half-Life and Anti-Tumor Activity

Recombinant Immunotoxins (RITs) are chimeric molecules composed of an antigen binding domain and toxin. The antigen binding domain component targets the cancer cell and delivers the toxin component to the cell. However, the efficacy of RITs is limited by their short half-life once they are in the patient. To address this problem, investigators at the National Cancer Institute (NCI) increased the half-life of RITs using polyethylene glycol (PEG).In specific embodiments, the antigen-binding fragment targets mesothelin, and the toxin is a fragment of Pseudomonas exotoxin (PE). Mesothelin is highly expressed in many human cancers including mesotheliomas, ovarian cancers, squamous cell carcinoma and pancreatic cancers – making it an excellent candidate for targeted therapies. The resulting PEGylated RITs have an increased half-life while retaining cytotoxic activity, thus increasing anti-tumor activity in mouse models. This indicates that site-specific modification with PEG can improve the therapeutic utility o f RITs. Furthermore, the ability of PEGylation to increase the half-life of RITs can be applied to other RITs directed against different targets.The NCILaboratory of Molecular Biology is seeking parties interested in co-development research collaborations and/or licensing of this technology for commercialization in the field of recombinant immunotoxins and cancer therapeutics.  IC: NCINIH Ref. No.: E-179-2019Advantages: Circulating half-life of RIT ’s im...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research