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“Extraordinary Finding!”--Malaria Plasmodium Protein (VAR2CSA) Binds to Glycosaminoglycan Sugar Molecule in Placenta; Same Molecule Also Found in Most Cancers; Malaria Parasite Protein May Target Attached Anti-Cancer Drugs to 90% of Cancer Types

Scientists at the University of British Columbia (UBC), Vancouver Coastal Health, and the BC Cancer Agency have discovered a protein from malaria that could one day help stop cancer in its tracks. This new approach, which halted the growth of various tumors in mice, was based on a discovery by collaborators at the University of Copenhagen. While exploring why pregnant women are particularly susceptible to malaria and trying to develop a vaccine to protect the more endangered pregnant women, the Copenhagen researchers found that the mosquito-borne parasite produces a protein (VAR2CSA) that binds to a particular type of sugar molecule (a glycosoaminoglycan) in the placenta. That discovery led to another; that same sugar molecule is also found in most cancers, and yet seemingly not on normal, non-placental tissue in the body. This commonality is understandable, because both cancers and placentas grow rapidly, often pushing aside other tissues in the process. The Copenhagen and Vancouver researchers realized that the sugar molecule could be a target for anti-cancer drugs, and that the malarial VAR2SA protein could provide the tool for carrying such drugs to tumors. "Scientists have spent decades trying to find biochemical similarities between placenta tissue and cancer, but we just didn't have the technology to find it," said project leader Mads Daugaard, Ph.D., an Assistant Professor of Urologic Science at UBC and a Senior Research Scientist at the Vancouver Prostate Centre, part of the Vancouver Coastal Health Research Institute. "When my colleagues discovered how malaria uses VAR2CSA to embed itself in the placenta, we immediately saw its potential to deliver cancer drugs in a precise, controlled way to tumors." To test that theory, Dr. Daugaard and colleagues enlisted the expertise of Dr. John Babcook and his team at The Centre for Drug Research and Development (CDRD). They attached a novel toxin to VAR2CSA and treated hundreds of normal and cancer cell lines. The drug compound specifically targeted and killed more than 95 per cent of the cancer cell lines.

The drug was then tested on mice that were implanted with three types of human tumors. With non-Hodgkin's lymphoma, the treated mice's tumors were about a quarter the size of the tumors in the control group.

With prostate cancer, the tumors completely disappeared in two of the six treated mice a month after receiving the first dose.

With metastatic breast cancer, five of six treated mice were cured from metastatic disease. The mice showed no adverse side-effects, and their organs were unharmed by the therapy.

The results have been published in the October 12, 2015 issue of Cancer Cell. The article is titled “Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein.”

"This is an extraordinary finding that paves the way for targeting sugar molecules in pediatric and adulthood human cancer, and our groups are vigorously pursuing this possibility together," said Dr. Poul Sorensen, a UBC Professor of Pathology and Laboratory Medicine and Distinguished Scientist with the BC Cancer Agency and co-senior investigator on the study.

"There is some irony that a disease as destructive as malaria might be exploited to treat another dreaded disease," said Dr. Ali Salanti, a Professor of Immunology and Microbiology at the Centre for Medical Parasitology, at the University of Copenhagen.

“For decades, scientists have been searching for similarities between the growth of a placenta and a tumor. The placenta is an organ, which, within a few months grows from only a few cells into an organ weighing approximately two pounds, and it provides the embryo with oxygen and nourishment in a relatively foreign environment. In a manner of speaking, tumors do much the same, they grow aggressively in a relatively foreign environment,” says Dr. Salanti from the Department of Immunology and Microbiology at the University of Copenhagen.

Dr. Salanti’s team is currently testing a vaccine against malaria on humans, and, as noted earlier, it was in connection with the development of this vaccine that he discovered that the carbohydrate in the placenta was also present in cancer tumors.

Dr. Salanti immediately contacted his former fellow student and now cancer researcher, Dr. Daugaard. In collaboration, the two groups have generated results, which they hope will provide the basis for a drug against many cancers.

“We examined the carbohydrate’s function. In the placenta; it helps ensure fast growth. Our experiments showed that it was the same in cancer tumors. We combined the malaria parasite with cancer cells and the parasite reacted to the cancer cells as if they were a placenta and attached itself,” Dr. Salanti explains.

In collaboration, the two university research groups have tested thousands of samples from brain tumors to leukemias, and a general picture emerges to indicate that the malaria protein is able attack more than 90% of all types of tumors.

“We have separated the malaria protein, which attaches itself to the carbohydrate and then added a toxin. By conducting tests on mice, we have been able to show that the combination of protein and toxin kills the cancer cells,” Dr. Daugaard explains.

“It appears that the malaria protein attaches itself to the tumor without any significant attachment to other tissue. And the mice that were given doses of protein and toxin showed far higher survival rates than the untreated mice.”

“We have seen that three doses can arrest growth in a tumor and even make it shrink,” Ph.D. student Thomas Mandel Clausen elaborates. He has been part of the research project for the last two years.

It would appear that the only snag is the fact that the treatment would not be available for pregnant women.
“Expressed in popular terms, the toxin will believe that the placenta is a tumor and kill it, in exactly the same way it will believe that a tumor is a placenta,” Dr. Salanti states.

In collaboration with the scientists behind the discovery, the University of Copenhagen has created the biotech company, VAR2 Pharmaceuticals, which will drive the clinical development forward. The research teams working with Dr. Salanti and Dr. Daugaard are now working purposefully towards being able to conduct tests on humans.

“The earliest possible test scenario is in four years time. The biggest questions are whether it will work in the human body, and if the human body can tolerate the doses needed without developing side effects,” Dr. Salanti said.
“But we’re optimistic because the protein appears to only attach itself to a carbohydrate that is only found in the placenta and in cancer tumors in humans,” Dr. Salanti concludes.

In addition to Copenhagen-based VAR2 Pharmaceuticals, Vancouver-based Kairos Therapeutics is also developing the compound for clinical trials in humans, which, as suggested earlier, will likely take another three to four years.

[University of Copenhagen press release] [Vancouver Coastal Health Research Institute press release][Cancer Cell abstract]