Mesothelioma is a rare, yet aggressive cancer mainly caused by asbestos exposure. There are very limited options for treatment. This is especially true for elderly patients. Conventional therapies might not be the best option due to the person’s age and other health problems. Chimeric antigen receptor (CAR) T cell therapy shows promise when treating different cancers including mesothelioma. CAR-T cell therapy works by targeting antigens on specific tumors. It has been a challenge to target the mesothelin antigen, which is an antigen on mesothelioma cells. A new article looks at the latest advancements with CAR -T cell therapy for malignant mesothelioma and the future of the treatment for mesothelioma patients.
Another tumor specific antigen related to mesothelioma is MSLN. Initial trials with MSLN-targeted CAR-T cells showed low effectiveness, but they were considered safe. Recent reports about CAR-T cell therapy for mesothelioma are troubling. One study found that high activity of MSLN-directed CAR-T cell therapy led to severe lung issues. This is now concerning researchers about safety. New targets and strategies are needed to improve the safety and effectiveness of CAR-T cell therapies for mesothelioma.
Researchers are looking at new targets for MSLN. They are looking at FAP, pan-ErbB receptors (EGFR and HER2), and CSPG4. They are all showing promise in preclinical studies. A new study looked at HEG1 for CAR-T cell therapy. The therapy was tested on models of malignant mesothelioma and were showing good results. The specific epitopes of MSLN targeted by CAR-T cells can significantly affect their efficacy. CAR-T cells targeting membrane-proximal epitopes have shown good tumor infiltration and persistence. H15B6 CAR-T cells target a juxtamembrane epitope of MSLN. They caused complete remission in preclinical models, which outdid traditional CAR-T cells. The traditional cells target more distal epitopes.
Pairing CAR-T cell therapy with other treatments shows promise for the treatment of solid tumors like malignant mesothelioma. One way to go about treatment is to modify CAR-T cells. The modification adds proteins like PD-1 antibodies or interleukin-15 (IL-15) to boost their function. Another way is to use CAR-T cells with existing drugs like pembrolizumab, which is a PD-1 inhibitor. Early trials of these treatments have been successful. The strategies hope to increase the survival of CAR-T cell survival and their ability to fight tumors. They target the tumor microenvironment, which is very complex. This prevents tumor regrowth and helps with the effectiveness of treatments on solid tumors.
Researchers are working to improve CAR-T cell therapies. They are looking for better targets and better combinations. There is great potential in the use of CAR-T cell therapies, but there are also risks of severe side effects. This is true for highly active CAR-T cells. Current studies aim to find the best and safest targets and modifications of T cells. Recent progress includes using genetic knockouts. They help CAR-T cells fight exhaustion and improve their cancer fighting abilities. The targets SUV38H1 and DNMT3A are the most promising. They help boost CAR-T cells against solid tumors. Another approach is the use of PROTACS, which are a technology that could make CAR-t Cell therapy even better. Developing CAR-T cell therapy for mesothelioma in elderly patients is tough, but is still promising. New targets, optimized epitopes, and combined strategies all improve the treatment process. Safety in regards to the treatments is still a concern, but research and trials are still advancing, with the hope for better outcomes.
