Mesothelioma Resources & Research | 2000 to 2003
Description: The potential to harness the patient's immune system underlies the growing interest in cancer immunotherapy. Immunotherapy can be made more successful if we know how exactly tumor immune responses are induced. Dendritic cells (DC) are so-called sentinel cells that patrol the body for tumors and harmful antigens. These cells present tumor antigens to the immune system and are vital for inducing T-cell responses, thereby generating tumor-specific immunity. The use of DC immunotherapy for cancer in humans is in its earliest phases, but promising results have been seen in melanoma and some hematological cancers. Dr. Lambrecht and his team will test this approach for the first time in mesothelioma. As the preparation for beginning a clinical trial, many issues have to be addressed, such as the best way to load tumor antigen, the best source of DCs and the best way to inject cells. In this study, mesothelioma derived small vesicles (exosomes) will be used as a cell-free source to load tumor antigen on DCs. Optimal conditions for immunotherapy will be tested in vitro and in an in vivo mouse model of mesothelioma.
David T. Curiel, MD,
Description: Gene therapy utilizes two alternatives: Mutation compensation corrects the gene abnormalities which allow tumor development in the first place, while molecular chemotherapy delivers toxin genes to the tumor cells. Both alternatives are quite promising, but their success has been limited by the difficulty of delivering the therapeutic gene to the target cells (cell transduction) in quantities sufficient to be therapeutic, while limiting the transduction in healthy cells. The second method, molecular chemotherapy, usually uses as the "vector" (the method of delivering the gene) a virus which is nonreplicating. Unfortunately, this makes the transduction, which leads to the intended cell lysis (death), a terminal event for the virus or vector, thus preventing further transduction in neighboring tumor cells. Dr. Curiel, a renowned gene therapy expert, seeks to develop a conditionally replicative virus that would replicate only in transduced mesothelioma tumor cells, thus limiting its effect on normal tissue, and yet would replicate through a lytic cycle, thus producing progeny to infect neighboring tumor cells and thus multiply its effect.
Description: Clinicians at Brigham and Women's Hospital and elsewhere have developed the "tri-modal" or "multi-modal" treatment for mesothelioma -- surgical resection, chemotherapy, and radiation therapy. While this trimodal treatment dramatically improves 5-year survival in selected patients, the majority of even the most optimal patients ultimately succumb to local recurrent disease. This is consistent with the widely documented resistance of mesothelioma tumor cells to commonly used chemotherapy drugs such as cisplatin.
Description: Dr. Lu seeks to sensitize mesothelioma to existing treatment, in this case radiation therapy as opposed to chemotherapy. This project takes advantage of the fact that pleural mesothelioma is typically local. Metastases is relatively rare and the tumor usually progresses -- and ultimately causes death - intrathoracicly (within the chest). Thus, intrathoracic radiation could be expected to be an effective treatment strategy if a major obstacle -- radiation's toxicity to critical organs in the chest -- could be overcome
Description: In her study, Dr. Ohar hopes to address the problem that mesothelioma is usually diagnosed in its later stages of development. For example, it is often first misdiagnosed as congestive heart failure or pneumonia, and only after treatment attempts for these conditions have failed is the diagnosis of mesothelioma made. As a result of the late diagnosis, treatment options and effectiveness are limited.
Johann Sebastian de Bono, MD, PhD
Description: This cutting-edge study applies the new field of pharmacogenetics (improving chemotherapys effectiveness and lowering its toxicity by individualizing it to the patients particular genetic profile) to malignant mesothelioma. The study will examine Alimta (pemetrexed), the first anticancer drug shown to improve the survival of malignant mesothelioma patients.
Description: DNA methylation is a chemical modification of DNA that occurs in many cancers. It is one of the mechanisms by which so-called tumor-suppressor genes are inactivated in cancer cells. Recent research suggests that the pattern of DNA methylation is specific for different kinds of cancer, and therefore DNA methylation analysis is one of the most promising new areas of cancer diagnostics. The Laird-Offringa laboratory proposes to identify methylation patterns specific for mesothelioma, using state of the art technology developed at the
Raphael Bueno, MD
Description: Dr. Bueno and his research partners have discovered in initial experiments that mesotheliomas can be classified into three different categories based on the pattern of expression of a small number of genes. It turns out that the survival of patients after therapy for mesothelioma varies based on which subclass they belong to. The work Dr. Bueno and his team will perform through the MARF grant is directed at validating this predictive test in a larger number of patients. This improved means of classifying patients will hopefully allow physicians and patients to select treatment strategies for mesothelioma more rationally.
Description: To evaluate tumor response to therapy in mesothelioma patients, doctors must perform tedious and subjective manual measurements of tumor thickness for the many images acquired during a CT scan. Through this project, Dr. Armato will develop an automated, computerized system that will objectively provide doctors with quantitative measurements of mesothelioma tumor volume. Such measurements should contribute to better understanding and evaluating the effects and benefits of different mesothelioma therapies.
Robert Cameron, MD
Title: National Mesothelioma Data/Tissue Bank Pilot Project (Special Meso Foundation Initiated Project)
Joseph R. Testa, PhD
Description: Dr. Testa is studying a chromosomal site, 1p22, which is deleted in 75% of all mesotheliomas, and which is suspected to harbor tumor suppressor genes. The Human Genome Project has recently discovered the actual gene candidates that normally reside in this region. Dr. Testa, therefore, will study each of the candidates to determine which one is altered at the DNA level in mesotheliomas, so as to cause the loss of the tumor suppressor function. By identifying the altered or missing tumor suppressor gene through support from the MARF grant, Dr. Testa would be in an ideal position to seek support from the National Institute of Health for a large study to identify the gene's specific tumor suppressing function. A way to replace the gene, or duplicate its function, could then be developed.