Despite some interesting pilot experiments more than a century ago,
nucleic acid has only recently been added to the list of agents used for the prevention and
therapy of
cancer. Two distinct features of
nucleic acids are used for this purpose: in
DNA and
RNA vaccines, genetic information for pathogen- or
tumor-derived
antigens is delivered to the host who then produces the encoded
antigen and initiates an immune response. In
DNA adjuvants, immunostimulatory sequences (CpG motifs) present in
DNA of bacterial origin are used. Such sequences are delivered in the form of
oligonucleotides or within the sequence of
DNA vaccine. In addition, CpG
oligonucleotides by themselves have successfully been used to stimulate the immune system in an
antigen-independent manner for the treatment of experimental
tumors.
DNA and
RNA vaccines for the treatment and prevention of
cancer and other diseases suffer from two some shortcomings: insufficient immunogenicity and--in the case of
RNA--low stability. A variety of strategies are being explored to improve the efficacy of
nucleic acid vaccines (genetic
vaccines) especially for
self-antigens in the case of
cancer. Among the most recent improvements are self-replicating
RNA vaccines and replicase-based
DNA-vaccines in which
antigen expression is under the control of an alphaviral replicase. Despite highly promising results in many animal
tumor models the efficacy of
nucleic acid vaccines and adjuvants in the clinic remains to be seen.