Nucleic acid for the treatment of cancer: Genetic vaccines and DNA adjuvants

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 preve ntion and therapy of cancer. Two distinct features of nucleic acids are use d for this purpose: in DNA and RNA vaccines, genetic information for pathog en- or tumor-derived antigens is delivered to the host who then produces th e encoded antigen and initiates an immune response. In DNA adjuvants, immun ostimulatory sequences (CpG motifs) present in DNA of bacterial origin are used. Such sequences are delivered in the form of oligonucleotides or withi n the sequence of DNA vaccine. In addition, CpG oligonucleotides by themsel ves have successfully been used to stimulate the immune system in an antige n-independent manner for the treatment of experimental tumors. DNA and RNA vaccines for the treatment and prevention of cancer and other diseases suff er from two some shortcomings: insufficient immunogenicity and - in the cas e of RNA - low stability. A variety of strategies are being explored to imp rove the efficacy of nucleic acid vaccines (genetic vaccines) especially fo r self-antigens in the case of cancer. Among the most recent improvements a re 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 nucle ic acid vaccines and adjuvants in the clinic remains to be seen.