DNA for genetic vaccination and therapy.
DNA coding for an antigen can be directly injected into muscle or skin and stimulate an immune response against the expressed antigen. The genes expressed can be derived from pathogens (e.g. viruses or bacteria), and can either code for surface molecules, which are often the basis for conventional peptide vaccines, or from the more genetically stable internal proteins. The DNA mimics a real infection in that the antigens are produced intracellularly where they are correctly folded and where they can be presented to the immune system so that cytotoxic T cells are stimulated as a defense mechanism. The DNA is expressed at low, but long-lasting, levels which is presumably the mechanism of its efficacy. Details of the mode of action and improvements for efficacy need to be worked out. Preclinical animal studies looked very promising, but need to be verified in humans. The method is safe and simple; DNA can be easily produced and transported, and can be composed of various genes. Recently also tumor-associated antigens have been tested in preclinical animal models, for example against colon cancer and malignant melanoma. Combinations with immune modulators are being worked out for improved efficacy. Successful therapies with this kind of gene medicine would be much cheaper and therefore superior to viral vectors. However, improvements are still required to prove that hopes are justified.
Moelling
K
K
Institute of Medical Virology, University of Zürich, Switzerland.
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000235:genetics; D019496:Cancer Vaccines / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000628:therapy; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy; D007111:Immunity, Cellular; D008546:Melanoma, Experimental / Q000628:therapy; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D012449:Safety; D014376:Tuberculosis / Q000517:prevention & control; D014611:Vaccination; D019444:Vaccines, DNA / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*
D000941:Antigens; D019496:Cancer Vaccines; D019444:Vaccines, DNA