Each year, the Mesothelioma Applied Research Foundation (MARF) awards grants to a few potentially groundbreaking projects. Using a highly competitive, peer-reviewed process, the group’s Science Advisory Board chooses the most promising projects to fund. Five grants were awarded in 2013:
1. “Optimizing the Radiation Approach to Mesothelioma with Immunotherapy”
Dr. Marc De Perrot and his team at University Health Network in Toronto are working to understand how to activate a patient’s immune system through developing new treatments. The group feels that the traditional approach to treating mesothelioma — combining chemotherapy with radiation and “extrapleural pneumonectomy” (EPP) — has only limited benefits for patients. Their new treatment regimen, starting with a shorter, 5-day carefully targeted radiation program, followed by EPP the following week, shows promise. This type of radiation treatment provides better immune activation (seen when the immune system starts actively fighting tumors in the body) than standard radiation does. The research team will test their theory that this treatment could help patients most when used in combination with immunotherapy.
2. “Evaluating the Effect of Immunity on Outcomes of Patients with Mesothelioma”
Principal investigator Christian Ottensmeier and his team at the University of Southampton feel that cancer therapies that specifically target the immune system are the most effective, and the most likely to improve health outcomes for patients. They will use their MARF grant to increase their understanding of the effect of immune cells in fighting mesothelioma. They will try to identify specific immune “signatures,” or markers, that may help predict clinical outcomes and help in treating patients. The hope is that this knowledge will result in the development of new and better treatments for mesothelioma.
3. “Specific Immunotherapy for Mesothelioma by Use of a Bi-Specific TCR-like Antibody”
Tao Dao, MD, PhD, and his team at Memorial Sloan-Kettering Cancer Center are looking at immunotherapy as a promising treatment for mesothelioma. As of now, the most successful form of cancer immunotherapy uses “tumor-specific monoclonal antibodies” (mAb) that engage particular types of cells to kill the tumor. This mAb therapy is limited by the fact that it has not been able to attack WT1, a tumor-specific protein that is found in large quantities in mesothelioma patients. The problem has been that WT1 is embedded within the cells, and standard mABs are only able to recognize protein on a cell’s surface, not proteins that are located within a cell. The team has developed a first-of-its-kind mAB that is able to recognize the WT1 protein. Called ESK1, it has already proven to be potent in killing mesothelioma cells in animals. The grant will allow the team to test a new and more powerful form of ESK1, and they hope to use it in human trials.
4. “Endothelial Cell Protein C Receptor Attenuates Mesothelioma Progression”
Usha Pendurthi, PhD, of The University of Texas Health Science Center at Tyler has found in preliminary studies conducted in mice that a particular protein—the “endothelial cell protein C receptor,” or EPCR—suppresses tumor growth while also activating cancer-suppressing genes. The goal of the research project is to identify the mechanism by which EPCR suppresses tumor growth in mice, and to begin to determine the therapeutic potential of this protein in treating mesothelioma in humans.
5. “Novel Lactate Dehydrogenase Inhibitors for the Treatment of Mesothelioma”
Elisa Giovannetti, MD, PhD and her team at VU University Medical Center in Amsterdam recently developed a series of novel “N-hydroxyindole-based inhibitors,” which were effective at suppressing different tumor cells, including mesothelioma cells. Their research will further evaluate the potential therapeutic aspects of these inhibitors in the hope that their findings will increase the pace of new drug discoveries and support future clinical trials.
To date, MARF has awarded $8.7 million in support of 91 projects in six countries.