Induction of anti-tumor immunity by gene delivery

In vivo gene transfer is accomplished by two classes of vectors: viral and non-viral. Both of these systems have advantages and disadvantages, and the choice of vector used largely depends on the suggested application. As the success of any gene therapy approach is dependent on the delivery of DNA, methods to improve the efficiency of vector systems are critical. The development of naked DNA-based gene delivery systems is reviewed and the results of experiments designed to improve and optimize two of these systems (bioballistics and electroporation) are reported.; Cancers are created by the accumulation of genetic changes that result in the abnormal function of normal cellular processes. These changes can be the result of the accumulation of mutation or the activity of oncogenic viruses such as human pappiloma virus (HPV). Since cancer is at heart a disease of the genes, it is a good candidate for intervention by gene therapy and many clinical trials of gene therapy strategies for cancer are currently in progress. The ultimate goal of this work is the development of novel preventative and therapeutic strategies for HPV induced cervical cancer. One approach is to introduce genes that halt tumor growth or progression. The role of HPV in cervical cancer and gene therapy methods to prevent tumor growth are reviewed. Experiments designed to elucidate the mechanism of action of an antisense strategy designed to halt the progression of HPV+ cancers are described.; Two conditions are necessary for the generation of a strong anti-tumor immune response; an initiating event and a sustaining environment. However, during progression tumors develop ways to prevent either or both of these things from happening. Any successful therapy must find a way to provide an antigen for immune recognition and overcome this tumor-induced immunosupression. The following areas are reviewed: (1) effector mechanisms involved in anticancer immunity; (2) ways tumors evade immune detection; (3) gene therapy methods to kill tumor cells or overcome tumor-induced immune suppression. The results of experiments designed to develop a strategy to induce anti-tumor immunity by gene delivery is reported.; Early work in immunology suggested that immunization against cancers was a possibility. Successful identification of tumor antigens has led to the possibility of anti-cancer vaccination using peptides derived from these antigens. Unfortunately, most tumor antigens are self-antigens and immunization strategies must overcome the formidable obstacle of self-tolerance. The development of a lipid-based system for in vivo gene delivery, the discovery of tumor antigens, and strategies for cancer vaccination are reviewed. Finally, the results of experiments designed to modify this vector for use as an enhanced antigen delivery system are described.