Category: Treatments
Cancer Vaccine Shows Promise For Pleural Mesothelioma Patients
A new cancer vaccine that may stimulate the immune system of patients with malignant pleural mesothelioma is entering a new round of clinical testing after promising preliminary results.
The vaccine maker, Aduro BioTech, Inc., announced this month the enrollment of the first patient in a Phase 1B clinical trial for the vaccine CRS-207. Medical researchers at the National Cancer Institute in Bethesda, Maryland and the H. Lee Moffitt Cancer Center in Tampa are participating in the trial.
Malignant pleural mesothelioma is a cancer of the lining of the chest cavity caused by exposure to asbestos. Approximately 2,500 to 3,000 people are diagnosed with mesothelioma each year in the U.S. Most are older workers, retired workers and veterans exposed to airborne asbestos fibers at a workplace decades ago. Mesothelioma takes decades to appear after exposure, but then advances rapidly.
The human immune system is a key line of defense against mesothelioma tumors if medical researchers can harness it to attack cancer cells, using immunotherapy. The vaccine was created using genetically modified strains of Listeria, a common food-borne pathogen known to produce a potent immune response. Researchers at Aduro BioTech engineered the pathogen to make it safe for use as the vehicle for therapeutic vaccines.
An earlier trial using the vaccine showed promising results in prolonging the lives of patients with advanced cancer. While patients with end-stage cancer typically live only three to five months, six of 17 patients who received the vaccine in the initial trial lived 15 months or longer, according to results recently published in the medical journal, Clinical Cancer Research.
As part of the new trial, mesothelioma patients will receive two prime vaccinations with CRS-207 followed by treatment with the standard chemotherapy drugs, pemetrexed and cisplatin.
“This trial will evaluate our vaccine treatment for the first time in frontline cancer patients, and we predict a synergistic benefit to their standard chemotherapy,” said Dr. Dirk Brockstedt, senior vice president of research and development at Aduro.
The vaccine also is being evaluated in a randomized, Phase 2 trial involving patients with metastatic pancreatic cancer.
For more information about the clinical trial, visit ClinicalTrials.gov.
Mesothelioma Cases Increasing in Australia and United States
The first report of a new national registry of mesothelioma in Australia shows that 27 people per million population are diagnosed with mesothelioma. That is nearly double the incidence of mesothelioma in the United States. Still it likely represents an undercount of mesothelioma cases in Australia due to delays in coding some diagnoses. Australia has one of the highest rates of mesothelioma in the world, according to the report by Safe Work Australia, a government agency that promotes worker safety and health.
According to the report, men accounted for 85 percent of the reported cases of mesothelioma since the new registry became operational in July 2010. Three-fourths of the people with mesothelioma were 65 years or older when diagnosed. The most common diagnosis was malignant pleural mesothelioma, a cancer of the lining of the chest cavity. Pleural mesothelioma represented more than nine out of every 10 diagnoses.
The overall rate of mesothelioma has been increasing in Australia since 1982 when data on new cases first became available, according to the report. Similarly, a 2009 report by the National Institute for Occupational Safety and Health indicated that deaths from mesothelioma are still increasing in the United States, based on data from 1998 through 2005. The overall rate in the U.S. is 14 deaths per million population per year. But only a half dozen states in the U.S. have mesothelioma rates of 20 per million population or greater, according to NIOSH.
Building materials containing asbestos and other asbestos products were widely used in Australia just as in the United States in the decades after World War II. As of August 2012, there had been 310 deaths of people diagnosed with mesothelioma in 2011 in Australia. Mesothelioma is an aggressive form of cancer and many people are not diagnosed until the cancer has reached an advanced stage.
Construction workers and people in building trades and electrical trades had the highest likelihood of exposure to asbestos, leading to a mesothelioma diagnosis in Australia. Currently in the United States, an estimated 1.3 million construction workers and general industry workers are potentially being exposed to asbestos, according to the U.S. Centers for Disease Control.
Historically, Australia has been one of the world’s highest users of asbestos, which was mined down under. Because of the long lag time of 20 years to 50 years between exposure to asbestos and appearance of the disease, the report predicts that incidence of mesothelioma in Australia likely still increasing and has not peaked.
Gene Therapy Approaches Milestone; Potential To Cure Diseases Caused By Inherited Gene Defect
You can expect to hear a lot more about gene therapy as a treatment for serious diseases in the years head. Gene therapy is still an experimental treatment in the United States, but holds the potential to cure genetic disorders by replacing a defective gene with a corrected copy of the gene. As The New York Times noted, gene therapy neared a milestone this week.
The European Medicine Agency’s Committee for Medicinal Products recommended approval of a gene therapy medicine to treat lipoprotein lipase (LPL), a rare inherited disorder that involves a defective gene, according to a press release posted Friday on its website. Patients with the disorder cannot produce enough of an enzyme that breaks down fat and may experience life-threatening pancreatitis attacks
If the European Medicine Agency follows the committee’s recommendation, as is typical, the medicine Glybera would be the first gene therapy medication approved for authorization in European countries. No gene therapy has been approved so far in the United States.
Jeffrey Ostrove, chief executive of Ceregene, a gene therapy company in San Diego told The New York Times, that pharmaceutical companies have been reluctant to invest in developing gene therapy drugs because there are no approved medicines. Ostrove said that approval of a gene therapy medicine in western Europe has the potential to change the way gene therapy is viewed.
Researchers have been studying the effectiveness of gene therapy in treating various diseases in clinical trials since a breakthrough discovery in 1989 that an abnormality in one gene on a specific chromosome caused the disease cystic fibrosis. That was a huge discovery. It led to the premise that doctors could cure a patient’s disease by identifying an abnormal gene mutation and replacing the defective gene with a corrected copy. The concept isn’t hard to understand, but making it work is complex. The initial applications of gene therapy are likely to involve rare diseases that may be cured by replacing a single defective gene. Lipoprotein lipase is a good example of that.
Researchers are investigating the applications of gene therapy for treatment of cancer including mesothelioma, a cancer of the lining of the lung caused by asbestos exposure. The University of Pennsylvania has an ongoing gene therapy clinical trial for patients who are newly diagnosed with mesothelioma and patients whose cancer has not responded to other treatments. Patients receive a combination of chemotherapy and a new type of gene therapy called immuno-gene therapy that uses a modified common cold virus to trigger the patient’s immune system to destroy cancer cells. Penn doctors have been encouraged by the response of mesothelioma patients receiving the treatment, Dr. Daniel Sterman an associate professor at the University of Pennsylvania said.
Approximately 2,500 to 3,000 people in the United States are diagnosed with mesothelioma each year with symptoms typically appearing 30 to 50 years after asbestos exposure. The disease is incurable, though there are treatments including chemotherapy, radiation and surgery.
Most people diagnosed with mesothelioma are older workers, retired workers or veterans who were exposed to asbestos fibers in the workplace or military service. Microscopic asbestos fibers when inhaled can lodge in the lungs and remain there a lifetime causing inflammation that eventually leads to asbestos related disease.
Protein Linked to Tissue Inflammation Suggests New Approach To Treating Mesothelioma, University of Hawaii Researchers Say
Asbestos was used extensively at the Pearl Harbor shipyards during World War II and the decades afterward. Today, Hawaii has some of the highest rates of mesothelioma in the nation, according to cancer researchers at the University of Hawaii.
For more than a decade, researchers at the University of Hawaii Cancer Center have been deciphering the molecular processes that cause normal cells to tranform into malignant mesothelioma cells. In a study in the July issue of the scientific journal Cancer Research, they report that malignant mesothelioma relies on a particular protein known as HMGB1 to fuel the growth of tumors. Suppressing the protein may be key to a new approach for treating mesothelioma, which is notoriously difficult for doctors to manage.
Mesothelioma is a cancer of the lining of the chest and abdominal cavities. It develops from inhaling microscopic asbestos fibers that lodge in the thin tissue lining the body cavity causing inflammation that leads to cancer. People in jobs in which asbestos exposure is an occupational hazard such as mining, shipbuilding, maintenance, plumbing and electrical work have a higher incidence of asbestos-related disease.
Medical researcher Haining Yang, an assistant professor at the University of Hawaii, and colleagues have studied asbestos-related disease for more than a decade. In a series of research papers, the Hawaii cancer researchers have detailed how asbestos damages and kills cells through a process called programmed cell necrosis that leads to the release of a protein molecule called HMGB1.
Patients with mesothelioma have elevated levels of the protein in their blood. The researchers suggest the protein may play a critical role in transforming healthy mesothelial cells into cancer cells and fueling the growth of malignant tumors.
In the most recently published study, the researchers treated mice with malignant mesothelioma with antibodies aimed at suppressing the protein HMGB1. They observed that inhibiting HMGB1 reduced the growth of cancer cells and extended the lives of the mice. Their findings suggest that mesothelioma cells rely on HMGB1 and that removal of the protein may produce a therapeutic response in mesothelioma patients, suggesting a new approach for malignant mesothelioma treatment.
Mesothelioma takes the lives of about 3,000 people a year in the U.S. People typically develop mesothelioma symptoms 20 years to 50 years after exposure to asbestos. The incidence of mesothelioma has risen steadily in the last decade in some parts of the world, including Europe and China.
Gene Therapy Moves Scientists One Step Closer to a Mesothelioma Cure
Finding a cure for mesothelioma did not seem possible just several years ago. The asbestos-caused cancer is extremely aggressive, and the cancerous cells invade the lungs and spread throughout the body often rendering standard cancer treatments ineffective against the disease. However, with the recent advances in gene therapy, now being touted as the next frontier in medicine, there is new hope in the medical field that cures are on the horizon for patients with rare and incurable diseases such as mesothelioma.
Ricki Lewis, a New York-based geneticist and author, explores this “next frontier” in her latest book The Forever Fix. The book follows the journey of the use of gene therapy to restore the vision of a young boy who was nearly blind from a hereditary disorder. The doctors replaced the single defective gene in the New York boy’s eyes that prevented his eyes from using vitamin A to send visual signals to his brain. Once the defective gene was replaced, the boy’s vision was restored and no further treatments or surgery were required.
“The goal of gene therapy is to replace faulty instructions,” said Lewis, who has a Ph.D in genetics from Indiana University. “It’s not right for every disease. But it is an approach that can be considered some day along with drugs, surgery and everything else.”
Most rare diseases, of which there are nearly 7,000 in the United States, are caused by a single gene defect, making them better candidates for gene therapy, Lewis said. Cancers, however, are often caused by a combination of genes as well as environmental factors. In the case of mesothelioma, asbestos is known to cause the disease, but researchers now believe a person’s genetics may determine whether they will actually contract the disease.
Lewis points to a study led by Dr. Jill Ohar of Wake Forest University, first reported in Oct. 2009, where as part of a new mesothelioma clinical trial, her team is investigating whether a person’s genes increase the risk of developing mesothelioma. Ohar began her research when she found “that there is a strong tendency for mesothelioma to run in families and it tends to be associated with a family history of cancer, which suggests a genetic susceptibility.”
“Getting at the basis of why one person develops mesothelioma and another person doesn’t, that is going to hold a clue to really fighting it,” Lewis said. “Then we will know what to do the gene therapy on.”
Mesothelioma victims typically show disease symptoms years or even decades after exposure to asbestos in an industrial or manufacturing workplace. The disease is eventually fatal, but aggressive therapy may prolong the lives of patients who are diagnosed early. Hopefully soon, mesothelioma patients will enjoy long, productive lives through research on genetics.
Sources :
- The Forever Fix
http://us.macmillan.com/theforeverfix/RickiLewis - mesothelioma clinical trial
https://clinicaltrials.gov/ct2/show/NCT01590472?term=mesothelioma+and+genetics&rank=1
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