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Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

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Technical Report,30 Sep 2014,29 Sep 2015

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Johns Hopkins University School of Medicine Baltimore United States

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The progression of prostate cancer PCa to castrate resistant metastatic disease is an ominous diagnosis. To overcome tumor cell heterogeneity based therapeutic resistance of PCa, the IsaacsDenmeade laboratories have advocated the use of chemical engineering principles to modify potent killing toxins as molecular grenades, which are delivered systemically and selectively detonated thereby, liberating their killing toxin efficiently only within the extracellular microenvironment at cancer sites. The objective for this proposal is to use a bio-engineering approach to produce recombinant pro-toxins designed for specific cleavage by a defined protease whose high expression is restricted to the tumor microenvironment at sites of metastatic castration resistant prostate cancerCRPC. Results show 1 a recombinant protein consisting of human serum albumin HSA and proaerolysin PAcan be produced via a peptide linker specific to a protease specific to the tumor microenvironment. 2 Recombinant HSAPA shows efficacy in vitro and low toxicity in animal studies.

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