The Mesothelioma Applied Research Foundation announced the recipients of its most recent research grants cycle awards totaling $400,000. This brings the total mesothelioma research funded by the organization to $11.5 million. This funding is made possible by philanthropic support in the form of donations to the Foundation. To make a donation to the Foundation, please visit https://www.curemeso.org/donate.
The Foundation’s research funding program, which was modeled after that of the National Institutes of Health, consists of a rigorous double peer review, a process that grades and ranks projects based on merit. Only the best and most promising projects advance to become funded. The peer reviewers are all leading mesothelioma experts who serve on the organization’s Science Advisory Board. The review process also includes feedback from a panel of patients, caregivers, and those who have lost a loved one to mesothelioma.
The Foundation received 29 letters of intent, of which 11 were invited to submit a full proposal. Of those, the following projects were selected for funding. To view the full list of previously funded projects, click here.
- “Transcriptomic analysis of mesothelioma-associated fibroblasts: a human-based study,”Dr. Marcella Barbarino, SHRO Institute
Recent research has identified fibroblasts as crucial elements in the performance of tumor suppressive functions, or vice versa, in tumor-proliferating functions, depending on the molecular characteristics of different fibroblasts. In fact, these cells, which are present in abundance in the tumor microenvironment, are now thought to be part of the reason why some tumors are resistant to chemotherapy and/or immunotherapy. With this project, Dr. Barbarino seeks to study these cells in order to understand which ones hinder response to treatment and which support it. This knowledge would open the door to potential therapeutic strategies personalized to a patient’s specific tumor and tumor microenvironment characteristics.
- “Monoclonal antibody-drug-conjugate to target oncogenic ERK5 in mesothelioma,” Dr. Emanuele Giurisato, Università degli Studi di Siena
The tumor microenvironment and the cells that comprise it are increasingly seen as the key to understanding why certain tumors respond to treatment while others don’t. The researchers in this study have already identified the process by which special cells present in the tumor microenvironment, called tumor-associated macrophages (TAMs), communicate with the tumor, and ultimately cause the expression of ERK5. This communication comes in the form of activation of a series of pathways in tumor cells that have been identified as chemoresistant. This study will test an antibody-drug conjugate (a concept for drug delivery directly into certain cells, akin to a trojan horse, which first binds to the cell and then releases the drug molecule into it) that would inhibit the activation of those tumor-inducing pathways.
- “Vaccine boosting to engage CAR T and endogenous T cells for long-term control of mesothelioma,”Dr. Leyuan Ma, Children’s Hospital of Philadelphia
Although CAR T cell therapies have shown much promise, just like other therapies for mesothelioma, they have faced significant challenges. Specifically, this type of therapy hasn’t been able to produce the expected results due to several factors, one being that the engineered cells don’t persist for very long in the body in the amounts necessary to make a difference, and the other is that the mesothelioma tumor itself may express mesothelin (the target of CAR T cells in mesothelioma treatment) in some parts of it, but not others. The team at UPenn has already identified a vaccine that works in conjunction with the CAR T cell process in other cancers that not only expands the CAR T cell numbers, but that also enhances the CAR T cell functionality and activates the patient’s immune system against the tumor. This same team is now looking to apply this knowledge to develop the equivalent type of vaccine for CAR T cells targeting mesothelin.
- “Localized immunotherapy for malignant pleural mesothelioma,”Dr. Dawen Zhao, Wake Forest University Health Sciences
This is another study aiming to bypass the challenges of the exceedingly complex tumor microenvironment. In fact, this study utilizes a new, just-developed, technique of delivering an immunostimulant directly into immune cells through a nanoparticle injected locally into the pleural or peritoneal cavity. In combination with FDA-approved immunotherapy (nivolumab + ipilimumab also known by the trade name of Opdivo + Yervoy), this nanoparticle therapy will be tested in mouse models to understand the immune effects on cells in the tumor microenvironment of mesothelioma.
