Abstract
The inoculation of plasmid DNA coding for a protein antigen by means of a simple intramuscolar (i.m.) or intradermal injection, or the more sophisticated "gene gun", currently represents an easily performed vaccine approach that is safe for host and relatively inexpensive. DNA vaccines have been described to generate humoral as well as cellular immune responses in various preclinical models of infectious and noninfectious diseases, such as autoimmune deseases and tumors, and also induced immunological memory. As this vaccine modality is still quite young, further study is needed to assure that when transferred to a clinical setting it will obtain results similar to those observed in animals. Our research group has studied the potentialities of this approach in the field of tumor immunotherapy. We utilized three different experimental tumor models to study the immune response induced by some DNA vaccines encoding proteins with characteristics similar to tumor-specific or differentiation antigens identified in human neoplasias. We observed that i.m. injection of a plasmid coding for a tumor antigen generated a specific immune response that was measurable in vitro as cytotoxic activity against antigenically correlated tumor cells. This response was efficacious in protecting a high percentage of animals from a subsequent tumor challenge, but was therapeutic only in very few tumor-bearing animals. Moreover, preventive immunity was even observed when animals were immunized with a differentiation antigen also expressed by cells of the tissue from which the tumor originates, thus indicating that the vaccination with DNA was able to break the state of central or peripheral tolerance that normally is established against a self antigen. Finally, we could demonstrate the immunogenic capacity of a plasmid that encodes a subdominant epitope of the tumor specific response, and compared it with that generated by a plasmid encoding the immunodominant epitope. This finding constitutes the premise for the potential use of subdominat epitopes in constructing DNA vaccines that would be particularly useful against tumor variants that have lost the expression of the immunodominant antigen or of the MHC molecule required for its recognition by T lymphocytes.