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 . 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  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 either 25 or 50% of prostate tissue respectively. This extensive damage was confined to the prostate with no toxicity observed in any other normal tissues, including those adjacent to the prostate such as the bladder, urethra, rectum and seminal vesicles. Furthermore, two weeks after the injection, we saw a disappearance of the toxin, but the continued presence of dead tissue, suggesting that the toxin's effects could be long lasting.
"Our observations suggest that injections into the prostate of this engineered, PSA-activated protoxin might have potential in treating men with locally recurrent or advanced prostate cancer, or for those with BPH where the protoxin could be used to reduce the size of the enlarged prostate," said Professor Denmeade. "A phase I clinical trial is in progress now for men with locally recurrent prostate cancer after definitive radiation therapy."
At the moment, the therapy involves injecting the protoxin directly into the prostate. "As such, its application is limited to men with recurrent disease after radiation who still have prostates. If it were to work very well it might be used earlier, in combination with other treatments, most likely radiation. In addition, the toxin is also under consideration as treatment for BPH. We hope that we will be able to further modify the toxin to make a systemic form that could be used to treat advanced prostate cancer in the future."
The study is treating the third cohort of patients and interim results are expected to be available at the end of the year.
PA is an inactive precursor of a bacterial protein that kills cells by forming large pores in the cell membrane. PRX302 kills the cancer cells in the same way when activated by PSA. The idea for this approach to treating prostate cancer came when Prof Denmeade, who had been working for some time on ways to harness the activity of PSA with drugs, heard about PA. "We called Dr Buckley , who is the world expert on PA, and discussed our strategy. Within two weeks he had generated the toxin and then we tested it for toxicities against a variety of cancers in our lab before starting our studies in prostate cancer."
Emma Mason | EurekAlert!
Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society
127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Power and Electrical Engineering
18.01.2017 | Materials Sciences
18.01.2017 | Life Sciences