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news.In laboratory tests, scientists have reportedly succeeded in reducing the resistance of ovarian cancer tumor cells to a natural resistance mechanism with the help of a monoclonal antibody.
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According to a research conducted by a group of scientists in partnership with professor Michael Krainer, director of the molecular genetics working group, department of oncology, University Clinic for Internal Medicine I, Vienna General Hospital, a new therapeutic agent for the treatment of particularly aggressive ovarian cancer has produced some good initial findings.
The project was funded by the Austrian Science Fund FWF. The project also succeeded in establishing a hitherto unfamiliar relation between so-called ‘natural killer cells’ and the regulated death of cancer cells.
A mechanism found in the bodies of higher organisms, known as ‘regulated cell death’ or apoptosis, actually eliminates potentially harmful cells. The human body also has a protective mechanism of this kind that acts against ovarian cancer cells. The mechanism is initiated by the messenger substance TRAIL (Tumor Necrosis Factor Related Apoptosis Inducing Ligand) which binds to receptors on tumor cells and triggers a suicide program.
The fact that ovarian tumors develop despite this, making ovarian cancer the most fatal form of the diseases affecting the female sexual and reproductive organs, is due to resistance to TRAIL: some tumor cells simply fail to react to the suicide signal.
A monoclonal antibody, which is a special protein that identifies cell structures with a high degree of specificity has provided significant assistance in this task. The antibody in question, which is known as AD5-10, binds particularly to the receptors that usually receive and transmit the TRAIL signal.
Professor Krainer said: “In addition to studies, in which TRAIL itself is used as a therapeutic agent, so-called monoclonal antibodies are also being researched which, like AD5-10, bind to the TRAIL receptor.
“Yet they can only trigger a suicide signal if there is no resistance to TRAIL. AD5-10 is special, however, because, although it binds to the TRAIL receptor like the other monoclonal antibodies, it does not bind at the precise location where the TRAIL itself docks. Therefore, AD5-10 can arise bound to the receptor along with TRAIL.”
His team has proposed a hypothesis that takes into account the unique binding site of AD5-10 to the receptor. It is possible that, due its special point of action, AD5-10 can influence the effect of TRAIL and perhaps also counteract resistance.
Professor Krainer added: “It actually works! We were able to show in both cell cultures and animal models that TRAIL-resistant ovarian cancer tumor cells become sensitive to TRAIL again if TRAIL and AD5-10 are both present at the same time.”
Additionally, Professor Krainer suspected that AD5-10 could reinforce the effect of drugs frequently used in chemotherapy. Hence, he examined the interaction between AD5-10 and numerous drugs used in the treatment of ovarian cancer.
He said: “We were able to show in cell cultures that the combined effect of AD5-10 and carboplatin – a common chemotherapeutic agent – was greater than the sum of their effects when administered individually. Moreover, tests on animal models showed that AD5-10 can eliminate resistance to carboplatin.”
Professor Krainer’s team also observed that the anti-tumor effect of AD5-10 only arises when the natural killer cells (NK Cells) are found in the tumor microenvironment. According to him, this is a good indication of the fact that these cells play an important role in apoptosis, as initiated by AD5-10.