Mesothelioma is a rare and aggressive cancer mainly caused by asbestos exposure. With the disease being rare, there are limited treatment options for the disease. This is especially true for elderly patients. They can struggle with conventional therapies due to their age and health problems. One therapy known as Chimeric antigen receptor (CAR) -T cell therapy has shown promise in treating different cancers, including malignant mesothelioma. The therapy works by targeting tumor specific antigens. It has been tough to treat mesothelioma because the concerning mesothelin antigen. A new article looks at the latest advancements in CAR-T cell therapy for malignant mesothelioma and what the future could look like for patients.
Mesothelin is a popular tumor antigen for mesothelioma. Initial trials for Mesothelin targeted CAR-T cells showed low effectiveness but were considered safe. Recent reports, however, are troubling. One study found that high mesothelin directed CAR-T cell activity led to severe lung issues. This sparked safety concerns. This proves that we need new targets and strategies to improve the safety and effectiveness of CAR-T cell therapies for mesothelioma. Researchers want to find other targets besides mesothelin. They are looking at FAP, pan-ErbB receptors (EGFR and HER2), and CSPG4. They show promise in preclinical studies. Another recent study focused on HEG1, for CAR-T cell therapy. The therapy was tested on models of malignant mesothelioma with good results. The specific epitopes of mesothelin targeted by CAR-T cells can greatly impact their efficacy. CAR-T cells targeting membrane-proximal epitopes have shown advanced tumor infiltration and persistence. One example is that h15B6 CAR-T cells target a juxta membrane epitope of mesothelin. This caused complete regression in preclinical models, doing better than traditional CAR-T cells. The traditional cells target further epitopes.
Combining CAR-T cell therapy with other treatments shows promise for treating solid tumors like malignant mesothelioma. One way is to modify CAR-T cells. This modification adds proteins like PD-1 antibodies or interleukin-15 to boost their function. The other option is to use CAR-T cells with existing drugs, like pembrolizumab, a PD-1 inhibitor. Early trials of this combination have been successful. These strategies look to improve CAR-T cell survival and their ability to fight tumors. They target the complex tumor microenvironment, which then leads to regrowth, and limits the effectiveness of treatments on solid tumors.
Researchers are continually improving CAR-T cell therapies. They do this by looking for new targets and better drug combinations. This therapy has the potential to improve many lives, but can also cause many side effects, especially for highly active CAR-T cells. Current studies look to find the safest, most effective targets and modifications. Recent progress includes the use of genetic knockouts, which help CAR-T cells fight exhaustion and improve their cancer fighting abilities. Targets like SUV39H1 and DNMT3A are promising because they boost CAR-T cells against solid tumors. Scientists are also looking at PROTACS, which have the potential to improve CAR-T cell therapies even more.
Developing CAR-T cell therapies for elderly mesothelioma patients is tough but shows promise. New targets, optimized epitopes, and combined strategies all improve the treatment. Safety is still a concern, but research is continuing to advance, helping create better outcomes. For the elderly and their caregivers, being informed and updated is essential. Thanks to these advancements, mesothelioma treatment could be changed for the better.
