Accession Number:

AD1047261

Title:

A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

Descriptive Note:

Technical Report,30 Sep 2014,29 Sep 2016

Corporate Author:

Johns Hopkins University Baltimore United States

Personal Author(s):

Report Date:

2016-12-01

Pagination or Media Count:

19.0

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 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 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 HSAPA shows efficacy in vitro and low toxicity in animal studies.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE