“Immunotherapy with a live bacterium combined with chemotherapy demonstrated more than 90% disease control and 59% response rate in patients with malignant pleural mesothelioma (MPM), according to the results of a phase Ib trial presented today at the European Lung Cancer Conference (ELCC) 2016 in Geneva, Switzerland.
“ ‘Malignant pleural mesothelioma is a cancer of the lining of the lung and is rare but difficult to treat,’ said Prof Thierry Jahan, professor of medicine at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, US. ‘Standard of care treatment with pemetrexed and platinum compound chemotherapy gets a 30% response rate but a modest impact on survival. So there is a clear unmet need in targeting this specific population.’
“Patients with MPM strongly express the mesothelin antigen in the tumour. CRS-207 is a live, attenuated Listeria monocytogenes bacterium that contains two gene deletions to diminish its pathogenicity and has also been engineered to express mesothelin.”
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“A new statistical model may help predict which patients are most likely to receive life-extending benefits from surgical treatment for malignant pleural mesothelioma (MPM), according to an article in the September 2015 issue of The Annals of Thoracic Surgery.
“MPM is an aggressive cancer that affects the lining of the chest cavity (pleura). The main cause of mesothelioma is believed to be repeated exposure to asbestos, which is a naturally occurring group of minerals found in soil and rocks around the world. Asbestos was previously used to make fireproof materials, such as theater curtains, insulation, flooring, and workers’ gloves, and is still used in some products today. About 3,000 cases of mesothelioma are diagnosed in the US each year, with many more worldwide. There is frequently a lag time of twenty years or more between exposure to asbestos and the development of the disease.
“Currently, there is no cure for advanced stage mesothelioma, and the 5-year survival rate is only about 10%.”
“Scientists have identified four biomarkers that may help resolve the difficult differential diagnosis between malignant pleural mesothelioma (MPM) and non-cancerous pleural tissue with reactive mesothelial proliferations (RMPs). This is a frequent differential diagnostic problem in pleural biopsy samples taken from patients with clinical suspicion of MPM. The ability to make more accurate diagnoses earlier may facilitate improved patient outcomes. This new study appears in the Journal of Molecular Diagnostics.”
Editor’s note: Diagnosis of cancer is not always straightforward. New techniques allow doctors to use the molecular/genetic characteristics of a tumor to more quickly and accurately diagnose cancer. In the research described here, scientists identified new molecular characteristics (“biomarkers”) that could be used to help identify mesothelioma tumors.
“Aduro BioTech, Inc., a clinical stage biotechnology company, today announced the presentation of safety and efficacy data from a Phase 1b clinical trial of its novel immunotherapy CRS-207 in combination with standard chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). Of the 16 evaluable patients, 69% (11/16) had confirmed durable partial responses (PR) with 25% (4/16) experiencing stable disease (SD) after CRS-207 and chemotherapy. The results were presented by Raffit Hassan, M.D., co-chief of the Thoracic and GI Oncology Branch at the National Cancer Institute, in a poster presentation at the 2014 American Society of Clinical Oncology Meeting (ASCO) held in Chicago.”
Editor’s note: Scientists have developed a new drug called CRS-207 for treating mesothelioma. CRS-207 is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. A clinical trial testing CRS-207 in volunteer patients found promising results for the drug.
Schuberth PC, Hagedorn C, Jensen SM, Gulati P, et al. Journal of Translational Medicine. Aug 12, 2013.
Malignant pleural mesothelioma (MPM) results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy.
FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells.