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Engineered Cellular Therapies for the Treatment of Thoracic Cancers.

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December 2024

Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.

Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses.

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Mesothelioma is a lethal cancer of the serosal lining of the body cavities. Risk factors include environmental and genetic factors. Asbestos exposure is considered the principal environmental risk factor, but other carcinogenic mineral fibers, such as erionite, also have a causal role.

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Primary pericardial mesothelioma is a highly aggressive and rare neoplasm that arises from the pericardial mesothelial cell and has a poor prognosis. The diagnosis is usually established by histological and immunohistochemical studies. Malignant mesothelioma most frequently occurs from the pleura (90%), less frequently from the peritoneum and pericardium (6%-10%), and very rarely from the tunica vaginalis in the testis.

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Background: In malignant pleural mesothelioma), it is difficult to evaluate the degree of tumor progression using imaging findings. It is essential to develop an objective index that is independent of imaging findings and useful for assessing the degree of tumor progression and indications for surgery.

Methods: We retrospectively evaluated the data of 79 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy or pleurectomy/decortication at our institution between 1999 and 2022.

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This review aims to summarize recent studies and findings within adoptive cell therapies, including tumor-infiltrating lymphocytes, genetically engineered T cell receptors, and chimeric antigen receptor T cells, in the treatment of thoracic malignancies, including non-small cell lung cancer, small cell lung cancer, and malignant pleural mesothelioma. Several trials are ongoing, and a few have reported results, suggesting that adoptive cell therapies may represent a potential treatment option for these patients, especially when checkpoint inhibition has failed. We also discuss the potential implementation of these therapies, as they present a new toxicity profile and an intrinsic financial burden.

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