Alphavirus Vectors as Tools in Cancer Gene Therapy

Alphavirus vectors, particularly those based on the replicon of Semliki Forest virus, have shown great potential as gene delivery vehicles for various applications in cancer gene therapy. The rapid production of high-titer recombinant SFV particles, which show impressive transduction rates in various mammalian cell lines, primary cultures and in vivo, results in high levels of transgene expression. Additionally, SFV vectors induce apoptosis in transduced host cells, which can further increase their efficiency in tumor therapy. Because of the broad host range some attempts to target the gene delivery have been engineered for Sindbis virus vectors, where IgG binding domains of protein A have been introduced into the envelope structure of the recombinant particles to allow attachment of virus to host cells through the interaction of protein A with monoclonal antibodies. SFV vectors have also been employed for the production of retrovirus-like particles for establishment of long-term gene expression. Tumor vaccine approaches have been taken by injection of SFV vectors as naked RNA molecules, DNA plasmids or recombinant particles to achieve both therapeutic and prophylactic efficacy. The continuous improvement of alphavirus vectors will further expand the application range in the future.