Albumin-proaerolysin prodrugs
AssigneeThe Johns Hopkins University
InventorsJohn T. Isaacs, Samuel R. Denmeade, W. Nathaniel Brennen
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Abstract
The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods for treating cancer using albumin-proaerolysin prodrugs. Accordingly, in one aspect, the present invention provides prodrug compositions. In certain embodiments, a prodrug composition comprises a prostate-specific antigen (PSA)-activated pro-aerolysin (PA), wherein a PSA cleavable linker replaces the native furin cleavage site within PA; and human serum albumin (HSA) or a fragment thereof fused to the N-terminus of the PSA-activated PA.
Claims10
A method of treating prostate cancer or benign prostatic hyperplasia (BPH) in a subject, comprising administering to the subject an effective amount of a prodrug composition comprising;
- a. a prostate-specific antigen (PSA)-activated pro-aerolysin (PA), wherein a PSA cleavable linker replaces the native furin cleavage site within PA comprising SEQ ID NO:
- 2;
- and
- b. human serum albumin (HSA), or a fragment thereof, fused to the N-terminus of the PSA-activated PA with a linker sequence comprising at least one PSA cleavable site,
- wherein the prodrug composition is administered systemically, and
- wherein the prodrug does not bind to GPI-anchored proteins on normal cells thereby lowering non-specific toxicity in subject tissues as compared to administration of the PSA-activated PA alone.
Dependencies are inferred from the claim text.