Category: Research
Vaccine May Enlist Body’s Immune System to Kill Mesothelioma Cancer Cells
Researchers at the Mayo Clinic and the University of Georgia have developed a vaccine that may offer a promising new strategy for treating various cancers including mesothelioma. An aggressive cancer associated with breathing asbsestos, mesothelioma originates most often in the lining of the lung and abdominal cavity.
The vaccine, which has shown dramatic results at reducing tumors in mice in laboratory experiments, helps a cancer patient’s immune system identify cancer cells and kill them, according to an article this week in the Proceedings of the National Academy of Sciences. Treatments that employ the body’s own defenses are known as immunotherapy. The research was funded by the National Cancer Institute.
Scientists have long sought to direct the immune system to distinguish when cells become cancerous by the distinct changes that sugars on the cell’s surface undergo. But since cancer cells originate within the body, the immune system generally doesn’t recognize them as foreign.
The vaccine identifies a special protein that is a signature of certain cancer cells. When malignant tumors occur, they produce the protein MUC1 at high levels, promoting the growth of tumors. Mesothelioma is among the types of cancer in which MUC1 is overexpressed, previous studies such as a 2008 study have shown.
“This is the first time that a vaccine has been developed that trains the immune system to distinguish and kill cancer cells based on their different sugar structures on proteins such as MUC1,” Sandra Gendler, a cancer researcher at the Mayo Clinic in Arizona and co-author of the study said in a press release.
The National Cancer Institute recently recognized MUC1 as one of the three most important tumor proteins for vaccine development, Dr. Gendler noted. MUC1 is found in more than 70 percent of lethal cancers including breast cancer, pancreatic cancer, ovarian, multiple myeloma, lung cancer and mesothelioma.
Geert-Jans Boons, a cancer researcher at the University of Georgia Cancer Center and developer of the vaccine, said the treatment, called MUC1 tripartite immunotherapy, produces a very strong immune response. The vaccine was shown to reduce tumors in mice by 80 percent or more, the researcher said.
The researchers are currently testing the vaccine’s effectiveness against cultured human cancer cells in the laboratory to assess toxicity. Phase I clinical trials involving cancer patients to assess the safety of the vaccine could begin in 2013.
Approximately 3,000 people are diagnosed with mesothelioma each year in the United States. Most are older workers, retired workers and veterans who were exposed to asbestos decades ago in the workplace.
Mesothelioma has a long incubation period, typically taking 30 to 50 years for symptoms to appear. When it does appear, the cancer is stubbornly resistant to conventional treatments such as chemotherapy and radiation and has a high fatality rate. So more effective treatments are urgently needed.
Catalog of Effects of Kinase Inhibitors May Aid Development of Anti-Cancer Drugs
Researchers at Fox Chase Cancer Center have catalogued the actions of 178 drugs that have the potential of blocking the activity of enzymes that promote growth of cancer cells, according to an article in the November issue of Nature Biotechnology.
The enzymes, called kinases, transmit signals and control complex processes in human cells. Kinases also function as drivers of a variety of forms of cancer, including mesothelioma. A number of studies suggest that kinases are involved in the gradual transformation of normal tissue in the lining of the lung into malignant pleural mesothelioma after exposure to asbestos. It’s unclear whether one or more kinases promotes the growth of mesothelioma.
More effective therapies and treatment options are needed for mesothelioma which is an aggressive cancer and has a low cure rate.
The scientists at Fox Chase Cancer Center in Philadelphia cataloged drugs including FDA-approved drugs, drugs undergoing clinical trial and laboratory compounds that are designed to block the cancer-promoting activity of any of more than 300 kinases. The body has more than 500 kinases that perform a variety of functions and many kinases are multi-taskers.
Drugs known as kinase inhibitors have the potential to be highly effective anti-cancer drugs that impede the cellular processes that cause cancer. Some cancer patients already receive kinase inhibitors as part of their therapy. And many additional kinase inhibitor drugs are under development. But the reactions of the drugs are complex.
Most kinase inhibitors act on more than one kinase. The drugs may disrupt both the growth of cancer and normal bodily processes at the same time, causing serious side effects such as heart problems.
With the cross-indexed catalog that the Fox Chase scientists have complied, researchers will be able to predict the complex reactions of the kinases inhibitors more accurately. That will allow for the development of drugs that block kinases that promote cancer while aiming to avoid side effects.
“These results have pushed the field closer to finding truly specific inhibitors of the processes that drive cancer,” Jeffrey R. Peterson, associate professor in the Cancer Biology Program at Fox Chase and senior author of the study said in a press release. “We now have a collection of kinase inhibitors that are more well-characterized and understood…. The next step is to use this information to identify specific, effective therapies that stop cancer in its tracks while avoiding healthy processes.”
Until the last few years, researchers didn’t have the tools to observe which kinase a drug acted upon. A new assay technology developed by Reaction Biology Corporation, a Pennsylvania-based provider of drug screening and profiling services, was used to catalog the kinase inhibitor effects.
Each year, approximately 2,500 to 3,000 people in the U.S. are diagnosed with mesothelioma. Most mesothelioma patients are older workers, retirees and veterans who were exposed to asbestos in the workplace. The use of asbestos is now restricted, but asbestos was widely use in the workplaces and in the military from the 1940s through the late 1970s.
Symptoms of mesothelioma typically take 20 years to 50 years to develop so a worker or veteran exposed to asbestos in the 1960s or 1970s may only recently have been diagnosed.
For more information about mesothelioma, click here.
Cancer Genetics Symposium Planned in Hawaii to Focus on Mesothelioma
Researchers in cancer genetics will gather in Hawaii in December to discuss the recent discovery of the BAP1 genetic mutation and its link to mesothelioma, melanoma and possibly other cancers. The University of Hawaii Cancer Center and the Queen’s Medical Center will host the international symposium on Dec. 2
Mesothelioma, a cancer of the lining of the lung or abdominal cavity, is typically associated with exposure to asbestos or erionite, a mineral fiber similar to asbestos. Microscopic fibers of asbestos are inhaled and may remain deep in the lung, causing inflammation, scarring and eventually disease.
The third annual Translational Cancer Medicine Symposium will feature more than 20 global experts on cancer genetics including Carol M. Croce, M.D., Director of the Human Cancer Genetics Program at Ohio State University; Joseph Testa, Ph.D., Director of the Genomics Facility at Fox Chase Cancer Center and Michele Carbone, M.D., Director of the University of Hawaii Cancer Center.
A mesothelioma research team at the University of Hawaii Cancer Center led by Carbone announced in August the discovery of BAP1 gene mutation’s link to mesothelioma and other cancers. It is the first study to demonstration that family genetics can influence susceptibility to mesothelioma.
“We are excited to bring these experts to Hawaii to work together to find ways to reduce the suffering and death caused by this mutation,” Cabone said in a prepared statement issued by the University of Hawaii Cancer Center.
Mesothelioma causes the deaths of about 2,500 to 3,000 people a year in the United States and tens of thousands worldwide. People typically develop mesothelioma symptoms 20 years to 50 years after exposure to asbestos, though only a portion of those exposed to asbestos develops mesothelioma. Rates of new cases of mesothelioma in parts of the world including Europe and China, have risen steadily in the past decade.
The identification of the BAP1 cancer syndrome, caused by an inherited mutation of the BAP1 gene, offers a new tool to identify people at high risk of developing mesothelioma. It may lead to early detection of the cancer and benefit people who have an occupational hazard of exposure to asbestos in the workplace. When individuals with the BAP1 mutation are exposed to asbestos, mesothelioma may cause the death of 50 percent of the family members—a far greater incidence than in the population at large, the researchers found.
Gene Testing May Eventually Transform Treatment for Mesothelioma Patients
In the future, patients with mesothelioma and other forms of cancer may receive medical treatment tailored to the genetics of their tumor. After all, cancer and other diseases stem from the complex interaction of multiple genetic and environmental factors.
Mesothelioma, a cancer of the lining of the lung, is closely associated with inhaling airborne asbestos fibers. Asbestos fibers lodge deep in the lungs causing inflammation that may cause genetic damage over time.
Mesothelioma produces an aggressive type of tumor. The median survival from diagnosis is just 12 months, creating a need for new treatment options to extend mesothelioma patients’ lives. Approximately, 3,000 people a year are diagnosed with mesothelioma. Many are retired workers and veterans who were exposed to asbestos in the workplace.
Cancer centers at large university-affiliated hospitals are starting to adopt genetic testing of tumors to understand tumors at a molecular level. Gene testing seeks to identify specific genes that may mutate and promote growth of cancer cells. When a gene contains a mutation, then the protein that the gene encodes is abnormal.
If doctors can identify a specific broken or mutant gene to target in a cancer patient, doctors then may be able to silence or “knock out” the troublemaker. Some cancer-causing genetic mutations switch the proteins that signals a cell to grow and divide —proteins called tyrosine kinases—to the permanent “on” position. Blocking tyrosine kinases has proven effective for treating certain human cancers including breast cancer, gastrointestinal tumors, leukemia and non-small cell lung cancer.
In a January 2011 article in the journal Neoplasia, researchers at Harvard Medical School reported on their research focused on trying to block certain proteins in 10 lines of mesothelioma cells. The researchers reported that the greatest reduction in the viability of the mesothelioma cells occurred when they blocked multiple types of receptor Tyrosine Kinases proteins rather than singling out individual proteins.
Genetic testing is changing doctors perception of cancer. Identifying the right gene to target may mean malignant tumors are treated more like an infectious disease after doctors understand the virus or bacteria that causes the disease.
Breakthrough in Using Immune System to Fight Cancer Through Gene Therapy
Researchers have long hoped to use the human immune system to kill malignant cancer cells. A new study in The New England Journal of Medicine suggests scientists at the University of Pennsylvania may have made significant strides in that approach using experimental gene therapy.
William Ludwig, a retired corrections officer from Bridgeton, N.J., volunteered for the experimental cancer treatment, because his chemotherapy had stopped working and he had few options, according to an article in The New York Times. Today, a year after the novel treatment, Ludwig’s chronic leukemia is in complete remission and he is playing golf and working in the yard. The same approach may work with other cancers besides leukemia, doctors say.
As part of the experimental treatment, the doctors removed a billion of Ludwig’s T-cells, white blood cells that fight viruses and malignant cells, and re-engineered them. They exposed the T-cells to a disabled form of the HIV-1 virus, which genetically altered the T-cells. They reprogrammed the T-cells to hone in on Ludwig’s leukemia and to reproduce in large numbers when activated by chemicals produced by malignant cells. They then reintroduced the T-cells into Ludwig’s blood.
Initially, Ludwig suffered flu-like symptoms such as a temperature and chills as the T-cells reproduced. The T-cells multiplied to 1,000 to 10,000 times the number infused, wiped out the cancer, then gradually diminished, leaving a rear guard of T-cells that can proliferate again if they sense more malignant cells. After a few weeks, Ludwig’s flu symptoms disappeared and there was no trace of the leukemia.
The doctors caution that the treatment is still experimental and are not yet claiming that Ludwig is cured. But a similar approach may work for treating other forms of cancer, the doctors say. Dr. Carl June, head of the research team at the University of Pennsylvania, plans to try the treatment approach on solid tumors produced by cancers such as ovarian cancer, pancreatic cancer and mesothelioma. Mesothelioma is an aggressive cancer of the lining of the lungs and abdomen closely associated with exposure to asbestos.
Approximately 2,500 to 3,000 people are diagnosed with mesothelioma each year in the United States. Many sufferers are retired workers and veterans who were exposed to asbestos decades ago, even if they didn’t realize it. Symptoms of mesothelioma typically appear 20 to 50 years after exposure, making the diagnosis more difficult.
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