PSMA Development Company, a joint venture of Progenics Pharmaceuticals and Cytogen Corporation, has released positive preclinical findings of its novel prostate cancer drug, PSMA ADC.
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In a mouse model of human prostate cancer, PSMA ADC (prostate-specific membrane antigen antibody-drug conjugate) significantly prolonged overall survival up to nine-fold as compared to untreated animals.
Remarkably, established tumors in two of the five animals treated at the highest dose were eradicated and remained undetectable over 500 days through the completion of the study. No overt evidence of toxicity was observed in any of these animal model tests.
Antibody-drug conjugate (ADC) drugs link a monoclonal antibody which targets specific cells in the body, such as cancer cells, with a cell-killing payload.
PSMA ADC is targeted to prostate cancer cells and incorporated into them, releasing the drug payload inside the cancer cell. The technology to link the PSMA monoclonal antibody to auristatin is being developed by PDC in collaboration with Seattle Genetics.
“Prostate-specific membrane antigen represents an excellent target in cancer therapy for many reasons. It is an integral membrane protein that is abundantly and preferentially expressed on the surface of prostate cancer cells,” said Dr Warren Heston, director, Research Program in Prostate Cancer, The Cleveland Clinic Foundation. “PSMA expression is high in prostate cancers that no longer respond to hormonal therapies and for which there are few treatment options.”
PSMA ADC was also tested in vitro and in animals for the ability to selectively eliminate prostate cancer cells. In laboratory studies, PSMA ADC killed PSMA-expressing prostate cancer cells at picomolar concentrations, whereas approximately 1000-fold higher concentrations were required to kill cells that lack PSMA.