Scientists design a PSA-activated protoxin that kills prostate cancer

Prague, Czech Republic -- Scientists have found a way of using a protein made by prostate cancer to target and kill the cancer cells themselves. In preliminary studies the new therapy affected only the prostate, without causing damage to other healthy tissues, and now it is being tested in a phase I clinical trial.

Prostate cancer is one of the commonest cancers in men, with nearly 680,000 new cases each year worldwide and more than 220,000 deaths [1]. Furthermore, by the age of 80, approximately 80% of all men will have developed a non-cancerous condition called benign prostatic hyperplasia (BPH) in which the prostate gland becomes enlarged. The findings reported today (Friday 10 November) have the potential to improve the survival and quality of life for men suffering from both these conditions.

Sam Denmeade, associate professor of oncology at John Hopkins University, USA, reported to the EORTC-NCI-AACR [2] Symposium on Molecular Targets and Cancer Therapeutics in Prague that he and his team3 had developed a protoxin, named PRX302, by modifying an inactive molecule, proaerolysin (PA). They engineered PRX302 to be activated by prostate-specific antigen (PSA) a protein made in higher than normal levels by prostate cancer. Once activated, they hoped that it would target and kill prostate cancer cells specifically.

He explained: "This represents a different kind of 'targeted' therapy, in that it seeks to use a protein made by the cancer to destroy itself."

Initial tests in the lab and in animals revealed that when the protoxin was injected into cancerous prostate tissue, it had a significant effect. "In the lab, PRX302 produced significant and often complete regression of the prostate cancer. Since the PSA gene is only found in primates and humans, we then injected either 0.35 or 4.1 micrograms as a single 25 microlitre injection into PSA-producing prostates of cynomolgus monkeys where it resulted in destruction of eit

Contact: Emma Mason
European Organisation for Research and Treatment of Cancer

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