What advances have you seen over the years in gene therapy for mesothelioma?
We have been conducting gene therapy clinical trials for malignant mesothelioma since 1995, initially using the so-called "suicide gene" HSV-TK and demonstrated safe and successful intrapleural gene transfer and evidence of clinical responses and some long-term (greater than 10 year) survivals with single dose treatment. Over the past 8 years, we have transitioned to intrapleural delivery of cytokine genes to stimulate local and systemic anti-tumor responses. Currently we are conducting several clinical trials of adenoviral-mediated interferon alpha gene therapy, both with intrapleural and intratumoral delivery. Our current Phase I trials involve two doses of gene vector alone; our Phase I/II trials involve combinations of interferon-alpha gene delivery with standard front-line chemotherapy (Pemetrexed/Cisplatin) or an accepted second-line regimen (Gemcitabine/Carboplatin). In 2012, we hope to initiate a trial involving neoadjuvant vector delivery followed by radical pleurectomy and intraoperative photodynamic therapy.
--Dan Sterman, MD, University of Pennsylvania Medical Center