This Phase I SBIR contract is to (1) produce multiple lots of GB13 to establish the quality and reproducibility of the manufacturing process, (2) characterize biochemical properties of GB13, including affinity to target cells, (3) qualify a live cell-based bioassay with multiple product lots, (4) develop a plan for Phase II SBIR preclinical development activities, including anmial efficacy and toxicity investigations to support the filing of an IND for human clinical trials. High-Grade astrocytomas (HGAs) are aggressive CNS tumor with median survival:::::: 14 months using the current standard of care. About 80% of HGAs overexpress an IL-13 receptor subunit [GB-13Ra(2)] that is virtually absent in healthy CNS tissue. GB 13 is a recombinant targeted cytotoxic fusion protein being developed to treat recurrent HGAs. Its targeting moiety, a single mutant human IL-13.E13K [Glu(13)-+Lys] binds GB-13Ra{2) with 50-fold higher affinity than native IL-13 and has low affinity for IL-13 receptor s of healthy tissue. It is linked to a mutant Pseudomonas endotoxin (PE4E), that is unable to bind its normal target cell receptor and can kill only cells that recognize IL 13.E13K. GB13 is a potent killer of cultured animal GBM cells in vitro. Targepeutics seeks funds to (1) produce multiple lots of GB13 to establish the quality and reproducibility of the manufacturing process, (2) characterize biochemical properties of GB13, including affinity to target cells, (3) qualify a live cell-based bioassay with multiple product lots, (4) develop a plan for Phase"""""""" SBIR preclinical development activities, including animal efficacy and toxicity investigations to support the filing of an IND for human clinical trials.
