UNMET NEED
The current standards of care for prostate cancer (Pca) include hormonal therapy, radiation therapy, surgery, chemotherapy, and combinational therapy. However, these treatments often have side effects that affect the quality of life of the Pca patients. Hence, there is an urgent need for developing better target-based therapies. This technology is a novel therapeutic that exploits the cytotoxic effects of a bacterial toxin, aerolysin, engineered to specifically target prostate tumor cells. Other advantages of this technology include:
• Enhanced targeting to tumor site using a naturally occurring and abundant human serum protein
• Decreased immunogenicity for prolonged potency
SOLUTION
Johns Hopkins researchers have developed a modified protoxin which more efficiently targets prostate cancer tumors using human serum album (HSA) for more potent and targeted tumor cell killing. The therapeutic will be composed of human serum albumin (HSA)-prostrate specific antigen (PSA)-proaerolysin (HSA-PSA-proaerolysin). Specifically, the protoxin will be made by fusing the C-terminus of HSA via a PSA cleavable peptide linker to the N-terminus of PSA proaerolysin to generate a novel recombinant fusion protein. The former developed toxin was toxic to cells due to its capacity to bind to GPI-anchored proteins found on normal cells in the blood or host tissues. The addition of the HSA fragment will inhibit the recombinant toxin from binding to GPI-anchored proteins. Instead, it will accumulate via an enhanced permeability and retention (EPR) effect within sites of metastatic prostate cancer where enzymatically active PSA in the extracellular fluid will hydrolyze the HSA linker liberating PSA-proaerolysin. Additionally, PSA will also remove the C-terminal inhibitory peptide from PSA-proaerolysin to generate aerolysin monomers which can oligomerize to form the heptameric pores that will result in selective primary killing of prostate tumor cells.
STAGE OF DEVELOPMENT
Preclinical stage of development
ASSOCIATED PUBLICATIONS
Oncotarget. 2012 Jul- 3(7)- 666–667Sci, Transl Med. 2012 Jun 27_4(140)_140ra86J, Natl Cancer Inst. 2007 Mar 7_99(5)_376-85,
Prostate. 2001 Jun 15_48(1)_1-6,
Eur Urol. 2011 May_59(5)_747-54
DISEASE INDICATION
Prostate Cancer
ASSOCIATED REPORTS OF INVENTION (ROIs) AND INTELLECTUAL PROPERTY (IP) FILING NUMBERS
Title: Albumin-proaerolysin prodrugs
Status: PCT Pending
Priority Date: 1/16/2015
IP Filing Numbers: 62/104,275 (publications: WO2016115415 A1)
