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Clin Respir J. 2019 May;13(5):272-279. doi: 10.1111/crj.13010. Epub 2019 Mar 24.

Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy.

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NYU Pulmonary Oncology Research Team (NYU PORT), Division of Pulmonary, Critical Care, and Sleep Medicine, NYU School of Medicine, NYU Langone Health, New York, New York.



Malignant pleural mesothelioma and malignant pleural effusions are a major therapeutic challenge, and are associated with impairment in quality of life and increased mortality. Advances in systemic therapies of malignant pleural mesothelioma have demonstrated limited clinical benefit and there is ongoing interest in intrapleural immunotherapies which have been demonstrated to be well tolerated overall with variable clinical responses. We have reviewed the literature to provide a comprehensive summary of novel intrapleural immunotherapeutic paradigms, including oncolytic virus therapy, gene-mediated cytotoxic immunotherapy, direct cytokine-mediated immunotherapies, innate immunomodulators and adoptive transfer of intrapleural chimeric antigen receptor T-cell therapy.


A review of PubMed for original manuscripts and conference reports published between 1998 and 2018 pertaining to intrapleural immunotherapy, as well as examination of reference lists from reviewed manuscripts.


Human clinical trials on intrapleural immunotherapies in subjects with malignant pleural mesothelioma or malignant pleural effusion were included in this review, including some relevant preclinical studies and anticipated ongoing trials reported on


Twenty-six clinical trials were identified, in addition to three trials currently in progress.


Intrapleural immunotherapies for pleural malignancy have demonstrated promise with regard to generating durable tumor-specific immune responses with possible clinical benefits which merit further investigation as part of multimodal chemotherapeutic and immunotherapeutic regimens.


Intrapleural immunotherapy; chimeric antigen receptor T-cell; gene-mediated cytotoxic immunotherapy; malignant pleural effusion; malignant pleural mesothelioma


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