Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer that arises from the mesothelial cells of the pleura. It is primarily caused by exposure to asbestos and has a poor prognosis. Standard treatment options include surgery, radiation therapy, and chemotherapy, but the response rates are generally low, and the disease often recurs. In recent years, immunotherapy has emerged as a promising treatment option for MPM. Immunotherapy aims to stimulate the immune system to recognize and attack cancer cells. This answer will discuss the most promising ongoing research efforts to improve the efficacy of immunotherapy in MPM.
Combination Immunotherapy
Combining different immunotherapies has shown promise in improving efficacy in various cancers. In MPM, several clinical trials are ongoing to evaluate the safety and efficacy of combining different immunotherapies. One such trial is the DREAM3R trial, which is evaluating the safety and efficacy of combining durvalumab (an anti-PD-L1 antibody) and tremelimumab (an anti-CTLA-4 antibody) in patients with MPM. Another trial is the CheckMate 743 trial, which is evaluating the combination of nivolumab (an anti-PD-1 antibody) and ipilimumab (an anti-CTLA-4 antibody) in patients with MPM. Preliminary results from the CheckMate 743 trial showed that the combination therapy improved overall survival compared to chemotherapy alone.
Personalized Immunotherapy
Personalized immunotherapy is an approach that aims to tailor the treatment to the patient’s specific tumor characteristics. It involves analyzing the patient’s tumor for specific biomarkers or mutations that can be targeted by immunotherapy. In MPM, several studies are ongoing to identify potential biomarkers that can predict the response to immunotherapy. One such study is the INFINITE trial, which is evaluating the efficacy of pembrolizumab (an anti-PD-1 antibody) in patients with MPM who have high levels of PD-L1 expression. Another study is the INITIATE trial, which is evaluating the efficacy of personalized immunotherapy based on the patient’s tumor mutational burden.
Adoptive Cell Therapy
Adoptive cell therapy involves engineering a patient’s own immune cells to recognize and attack cancer cells. In MPM, several studies are ongoing to evaluate the safety and efficacy of adoptive cell therapy. One such study is the MesomiCAR trial, which is evaluating the safety and efficacy of CAR-T cell therapy in patients with MPM. CAR-T cell therapy involves engineering the patient’s T cells to express a chimeric antigen receptor (CAR) that recognizes a specific protein on the surface of MPM cells. Another study is the ADP-A2M4CD8 trial, which is evaluating the safety and efficacy of ADP-A2M4CD8 TCR-T cell therapy in patients with MPM. TCR-T cell therapy involves engineering the patient’s T cells to express a T-cell receptor (TCR) that recognizes a specific protein on the surface of MPM cells.
Immunomodulatory Agents
Immunomodulatory agents are a class of drugs that can enhance the immune system’s ability to recognize and attack cancer cells. In MPM, several immunomodulatory agents are being evaluated in clinical trials. One such agent is the TLR9 agonist CMP-001, which is being evaluated in combination with pembrolizumab in patients with MPM. TLR9 agonists are known to stimulate the immune system by activating immune cells called dendritic cells. Another agent is the IDO1 inhibitor epacadostat, which is being evaluated in combination with pembrolizumab in patients with MPM. IDO1 inhibitors are known to enhance the immune system’s ability to recognize and attack cancer cells by reducing the production of an immune-suppressive molecule called kynurenine.
Conclusion:
In summary, immunotherapy has emerged as a promising treatment option for MPM. Ongoing research efforts are focused on improving the efficacy of immunotherapy by combining different immunotherapies, personalizing the treatment based on the patient’s tumor characteristics, using adoptive cell therapy, and using immunomodulatory agents. These approaches hold great promise in improving the outcomes for patients with MPM, but more research is needed to fully understand their potential and to identify the most effective strategies to use.
