Masaaki Tamura D.V.M., Ph.D.

Lay Description

Epidemiological studies indicate that lung cancer is the major cause of cancer-related deaths in the United States. Bronchioalveolar carcinoma (BAC), a subtype of lung cancer, often develops in the middle-age population without a history of tobacco smoking. Although efforts to develop early detection and subsequent surgical, chemotherapy and radiation-therapy strategies have been made, survival for subset of patients is still low. Therefore, effective new therapeutic approaches to this disease are urgently needed.

AC usually develops at multiple sites in the airway epithelial cells. Accordingly, this study is designed to treat multiple cancer sites by targeted gene therapy which will be delivered by genetically engineered adult stem cells. Our new method will deliver cancer cell toxic gene products to the cancer tissues in a high concentration without damaging normal tissues in the body.

Adult stem cells derived from umbilical cord matrix are relatively easy to prepare in large quantity and there is no ethical issue involved in the preparation procedure, since umbilical cord is no longer useful after the delivery. In this study, we will test our hypothesis that 1) genetically engineered adult stem cells that express cancer cell toxic interferon-β are specifically delivered to BAC sites; 2) the engineered stem cell significantly attenuates cancer growth of BAC; 3) this stem cell-based therapy does not damage any normal tissue.

Our treatment strategy is significantly better than existing therapeutic strategies, including surgical therapy followed by radiation and chemotherapies since we anticipate many fewer side effects. Our stem cell-based delivery system is specific to the cancer tissues that have preliminarily been examined. Our preliminary study also demonstrated that interferon-β expressing umbilical cord stem cells significantly attenuate cancer growth of metastatic breast cancer cells. Although this study will be conducted using the preclinical model, this procedure is easily applicable to human patients. Therefore, this study is feasible and our method has high potential for future human application.

Scientific Abstract

Bronchioalveolar lung carcinoma (BAC) is a subset of adenocarcinoma for which precise etiology is not known. Although a majority of adenocarcinoma is etiologically associated with tobacco smoke and other pollutants, a large portion of BAC occurs without tobacco smoking history. Most characteristic genetic predisposition associated with BAC is k-ras gene mutation. Despite early surveillance and development of new therapeutic agents, incidence of BAC is increasing and its prognosis is still poor. BAC is resistant to chemotherapy and radiation therapy. Gene therapy for lung cancer has been hopeful, yet clinically unsuccessful because of an insufficient cancer tissue-specific gene delivery. We recently demonstrated successful cancer tissue-targeted interferon (IFN)-ß gene delivery using adult mesenchymal stem cell prepared from human umbilical cord matrix (hUCMSC). Our preliminary data indicate that this stem cell-expressed IFN-ß substantially attenuated lung metastasized breast cancer xenografts in vivo. In this study, we will test our hypothesis that 1) genetically engineered adult stem cells which express cancer cell toxic IFN-ß are specifically delivered to BAC sites; 2) the engineered stem cell significantly attenuates BAC cancer growth in preclinical model with k-ras mutation; 3) this stem cell-based therapy does not damage any normal tissue. Our treatment strategy is significantly better than existing therapeutic strategies, including surgical therapy followed by radiation and chemotherapies, since we anticipate far fewer side effects. If our hypothesis is proven correct, although this study will be conducted using the preclinical model, this procedure will be applied to human patients in the future. Therefore, this study is feasible, scientifically valuable and has high potential for future human application.