Gene therapy for lung neoplasms

Abstract

SYNOPSISBoth advanced stage lung cancer and malignant pleural mesothelioma are associated with a poor prognosis. Although there have been advances in treatment regimens for both diseases, these have had only a modest effect on their progressive course. Gene therapy for thoracic malignancies represents a novel therapeutic approach and has been evaluated in a number of clinical trials over the last two decades. Strategies have included induction of apoptosis, tumor suppressor gene replacement, suicide gene expression, cytokine based therapy, various vaccination approaches, and adoptive transfer of modified immune cells. This review will consider the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies.

Gene therapy for malignant mesothelioma: beyond the infant years

“…3,6 Indeed, several gene therapy clinical trials have now been conducted. In fact, the first human gene therapy trial approved in the US as primary cancer treatment was aimed at mesothelioma.…”

“…3 The relatively inefficient delivery of transgenes in tumor tissue provides a compelling argument to further develop viral gene therapy vectors, since replication competent viruses have the capacity to spread through the tumor and amplify the transgene, in contrast to gene transfer via tumor cells or DC. Also, gene transfer via infection, mediated by viral particles, is more efficient than naked DNA transfection.…”

“…1 Thus, there is an urgent need for new therapeutic options, beyond chemotherapy and surgery, 2 one such approach is gene therapy. [3][4][5] The premise of gene therapy is that 'therapeutic' genes are administered into the tumor, upon which their expression in transfected tumor cells could alter the course of disease. For example, local expression of the transgenes could enhance sensitivity of tumor cells to therapy, change immune responses against the tumor, block angiogenesis or reverse the malignant phenotype of tumor cells.…”

Malignant Pleural Mesothelioma–Targeted CREBBP/EP300 Inhibitory Protein 1 Promoter System for Gene Therapy and Virotherapy

“…9]. However, no significant clinical responses were observed, indicating that improvements are critically needed in gene therapy approaches for the treatment of mesothelioma (10).…”

Assessment of p53 gene transfer and biological activities in a clinical study of adenovirus-p53 gene therapy for recurrent ovarian cancer

“…Extensive safety data and gene transfer information have also been reported by other investigators using recombinant adenoviral (rAd) gene transfer in various clinical trials. [8][9][10][11][12] While many of these initial protocols have demonstrated the feasibility of using recombinant adenovirus to deliver genes to tumors in humans, further investigation is required to understand the potential for effective gene therapy with this delivery system. In this study we investigated: (1) whether the gene was delivered to the tumors of human subjects using a recombinant adenovirus vector, (2) whether the delivered gene demonstrated the anticipated transcriptional activity of human p53 wt , and (3) whether repeat administration of a recombinant adenovirus will result in significant gene transfer.…”