A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer
Abstract
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 Isaacs/Denmeade 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 cancer (CRPC). Results show 1) a recombinant protein consisting of human serum albumin (HSA) and proaerolysin (PA) can be produced via a peptide linker specific to a protease specific to the tumor microenvironment. 2) Recombinant HSA/PA shows efficacy in vitro and low toxicity in animal studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2016
- Accession Number
- AD1047261
Entities
People
- Freddie Pruitt
Organizations
- Johns Hopkins University