Novel DNA vaccines for the treatment of lung cancer
Initial Award Abstract
Cancer of the lung and bronchus currently ranks second among the top ten leading sites and causes of cancer incidence and death among Californians, according to the California Department of Health Services. It is particularly alarming that from 1988-1996 the average annual rate of death per 100,000 population from this disease is highest among African-Americans in California, where it exceeds that of all other races by 39%, i.e. 61 versus 44 per 100,000 population. We plan to produce a vaccine against human lung cancer for which we have already obtained a proof of concept in a mouse model, where we demonstrated that a vaccine against carcinoembryonic antigen (CEA), widely distributed among lung carcinoma patients can prevent the onset of this cancer. Our aim is to further improve the efficacy of this vaccine and to design it so that it can also be used to treat existing lung cancer and prevent its recurrence, particularly in a setting of minimal residual disease. In other words, our aim is to prevent, or at least slow down, the spread (metastases) of lung cancer in patients who were treated by other means, e.g. surgery, but still had some persisting lung cancer metastases. Our aim is to achieve this by using a genetically engineered vaccine to strongly stimulate the body’s natural defense mechanisms, i.e. immunity against cancer cells. Since we are using a specialized mouse model system to evaluate our vaccine directed against an antigen, i.e. a molecular marker extensively expressed on human lung cancer cells, it is conceivable that our vaccine, once perfected in the mouse model, could rapidly enter clinical trials to critically evaluate its ability to treat human lung cancer in a minimal residual disease setting. Importantly, achievement of this research proposal’s objectives may not only aid in improving prevention and treatment of lung cancer, but may also serve as a model for developing new and effective DNA vaccines against other cancers, including those of the colon, breast and pancreas. |
|An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice
|Authors: Niethammer, A.G., Primus, F.J., Xiang, Dolman, Ruehlmann, Gillies, and Reisfeld, R.A.