Chiba University, Chiba, Japan
Copyright 2016, American College of Chest Physicians. All Rights Reserved.
SESSION TITLE: Lung Cancer IV
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM
PURPOSE: Malignant pleural mesothelioma is an intractable malignancy with poor prognosis. For unresctable cases, the median survival by chemotherapy with cisplatin plus pemetrexed, is only one year. We tested the safety and effectiveness of intra-thoracic injectionof adenoviral vector expressing NK4 gene.
METHODS: We planned to conduct a clinical study of gene therapy with adenoviruses expressing the NK4 gene (Ad-NK4) to control the local tumor growth. The study is designed to inject Ad-NK4 into the intrapleural cavity with a dose escalation manner from 1010 to 1012 virus particles per patient and to examine safety and possible clinical benefits.
RESULTS: We conducted animal experiments to examine the safety level as one of the preclinical studies, and showed that Ad DNA administered in the pleural cavity was detected in many parenchymal organs. Pathological analyses showed that liver damages were the major adverse effects with little toxicity to other organs. These studies firstly demonstrated biodistribution and transgene expression after an intrapleural injection of Ad vectors in an animal study, which contrasts with an intravenous injection showing relatively rapid clearance of Ad-NK4. The phase 1 clinical trial in human is on-going.
CONCLUSIONS: The clinical study can also provide information regarding production of NK4 protein and antibody against NK4. These data will be important to determine whether local production of NK4 molecules can be an anti-cancer strategy or not.
CLINICAL IMPLICATIONS: This is the first gene therapy for malignant pleural mesothelioma in Japan. These data are of great importance for the future clinical trial agai this rare malignancy.
DISCLOSURE: The following authors have nothing to disclose: Toshio Suzuki, Yuji Tada, James West, Koichiro Tatsumi, Masatoshi Tagawa, Kenzo Hiroshima, Hideaki Shimada
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