Abstract
Cancer is one of the most challenging diseases of today. Optimization of standard treatment protocols consisting of the main columns of chemo- and radiotherapy followed or preceded by surgical intervention is often limited by toxic side effects and induction of concomitant malignancies and/or development of resistant mechanisms. This requires the development of therapeutic strategies which are as effective as standard therapies but permit the patients a life without severe negative side effects. Along this line, the development of immunotherapy in general and the innovative concept of DNA vaccination in particular may provide a venue to achieve this goal. Using the patient's own immune system by activation of humoral and cellular immune responses to target the cancer cells has shown first promising results in clinical trials and may allow reduced toxicity standard therapy regimen in the future. The main challenge of this concept is to transfer the plethora of convincing preclinical and early clinical results to an effective treatment of patients.
Highlights
IntroductionPromising results were obtained with the use of self-replicating RNA and DNA vaccines which were able to break tolerance against tumor-associated self-antigens involving pathways of innate antiviral immunity
The superiority of xenogeneic vaccination approaches became obvious in a study were hgp100 plasmids were applied via helium-driven DNA-gold complexes leading to a tumor protection in many of the mice which was mediated by specific CD8+ T cells with the typical side effect of autoimmune depigmentation [118]
DNA vaccination is a young field in immunotherapy of cancer and has certainly not yet lived up to its expectations
Summary
Promising results were obtained with the use of self-replicating RNA and DNA vaccines which were able to break tolerance against tumor-associated self-antigens involving pathways of innate antiviral immunity These vaccines enhance the immunogenicity and production of antigen-specific antibodies and CD8+ T cells without negative side effects. DNA vaccines capable to activate the patient’s immune system to effectively target cancer need the activation of effector cells that are able to kill the tumor or can indirectly trigger a cascade that subsequently lead to its eradication. It is possible to increase the protection against virus or tumor challenge by directing the antigen to specific cell compartments like the proteasome leading to fast degradation and presentation of antigen to MHC class I molecules [87]. Ubiquitination of DNA minigenes probably leads to polyubiquitination of the cleaved peptide epitopes resulting in a more effective delivery of the minigene to the proteasome and an increase of the frequency of CTL precursors [24]
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