Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer
AssigneesUniversity of Victoria Innovation, Development Corporation, The Johns Hopkins University
InventorsSamuel Denmeade, John Isaacs, J. Buckley
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Abstract
Disclosed herein are modified proaerolysin (PA) peptide. In some examples, the proteins include a prostate-specific protease cleavage site and can further include a prostate-tissue-specific binding domain which functionally replaces the native PA binding domain. In other examples, the proteins include a furin cleavage site and a prostate tissue-specific binding domain which functionally replaces the native PA binding domain. Methods of using such peptides to treat prostate cancer are also disclosed.
Claims20
A purified peptide comprising a variant proaerolysin amino acid sequence, wherein the variation of the proaerolysin amino acid sequence comprises replacement of the furin cleavage site corresponding to the sequence of amino acids at positions 427-432 of SEQ ID NO:
- 2 by a prostate-specific protease cleavage site, wherein administration of 2.5 to 25 μg of the peptide to a mouse having a prostate tumor xenograft reduces the proliferative index of the tumor to less than 1%.
A purified peptide comprising a variant proaerolysin amino acid sequence, wherein the variation of the proaerolysin amino acid sequence comprises a functionally deleted proaerolysin binding domain corresponding to the sequence of amino acids at positions 1-83 of SEQ ID NO:
- 2 replaced with a prostate-tissue specific binding domain.
A purified peptide comprising a variant human perforin amino acid sequence, wherein the variation of the human perforin amino acid sequence comprises replacement of the wild type perforin activation site by a prostate-specific protease cleavage site.
Dependencies are inferred from the claim text.