Immuno-gene Therapy for Thoracic Malignancies
Lung cancer and other thoracic malignancies are the leading cause of cancer deaths in the United States today. The Thoracic Oncology Research Laboratory is focusing on the design of new treatment strategies for lung cancer and mesothelioma based on the rapidly evolving disciplines of molecular biology, immunotherapy, and gene therapy.
Dr. Albelda’s research is translational in focus and includes animal models, work with human tumor samples, and the conduct of clinical trials. This work is primarily funded through a recently renewed Program Project from the National Cancer Institute and participation in a number of RO1 grants.
The tumor microenvironment is one area of active study. Studies are underway with the goals of 1) a better understanding of the biology of the tumor microenvironment with a focus on the immunuosuppressive activities of white blood cells and fibroblasts, 2) novel approaches to alter the tumor microenvironment to enhance immunotherapy including studying effects using COX-2 inhibitors, TGFbeta inhibitors, T-regulatory cell inhibitors., antibodies against B-cells, and chemotherapeutic drugs. A second area of interest in the lab is the use of adoptive T cell transfer to treat lung malignancies. Studies are underway to modify T cells in order to make them traffic more efficiently into tumors, to have better killing function, and to resist inactivation by the tumor microenvironment. A T cells targeting cancer-associated fibroblasts is being developed. In addition, Dr. Albelda is closely involved with a number of immunogene clinical trials at Penn using an adenovirus expressing the immune-activator interferon-alpha that is instilled into the pleural space of mesothelioma patients (in collaboration with Dr. Daniel Sterman) and T cells altered to attack the mesothelioma tumor target, mesothelin (in collaboration with Drs. Carl June and Andrew Haas).
These mice will develop lung tumors with diffuse phenotype and massive fibrosis after giving a single dose of Ad.Cre to induce the mutation.