Cytokines and costimulatory molecules as genetic adjuvants

DNA vectors expressing an antigen derived from a pathogen or a cancerous cell have been shown, after inoculation into experimental animals, to trigger de novo synthesis of foreign proteins, which induce an immune response. This immune response can be modulated by coinoculation of vectors encoding either cytokines or costimulatory molecules. A variety of cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-2, IL-4, IL-12 and IFN-gamma, as well as the costimulatory molecule B7.1, have been tested to date for their ability to amplify the immune response to genetic vaccines. Although the results obtained thus far clearly show that coadministration of vectors expressing immunomodulatory molecules, such as cytokines, may increase the efficacy of genetic vaccines, this approach is currently considered unsuitable for use in human patients due to the potential side effects of persistent cytokine expression.