Gene therapy for lung neoplasms

Abstract

Both advanced-stage lung cancer and malignant pleural mesothelioma are associated with a poor prognosis. Advances in treatment regimens for both diseases 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 several clinical trials. 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 considers the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies.

Figure 1. Regression of mediastinal tumor after intrapleural Ad.IFNα

Panel A: Pretreatment PET/CT image demonstrating a pleural tumor nodule near the anterior mediastinum (circled), Panel B: Regression of nodule 6 months after treatment with Ad.IFNα.

Figure 2. Immuno-Gene Therapy Paradigm

This approach relies on only enough gene transfer to induce immunity and generate a strong bystander effect. The anti-tumor immune responses are augmented by complementary approaches to target large tumor volumes or the immunosuppressive networks present in most tumors.