Title:Application of Alphaviral Vectors for Immunomodulation in Cancer Therapy
Volume: 23
Issue: 32
Author(s): Anna Zajakina, Karina Spunde and Kenneth Lundstrom*
Affiliation:
- PanTherapeutics, Rue des Remparts 4, CH1095 Lutry,Switzerland
Keywords:
Alphaviruses, recombinant particles, RNA replicons, layered DNA vectors, immunotherapy, vaccines, gene therapy, cancer
therapy.
Abstract: Background: The lack of specific and efficient cancer therapies has influenced the development of
novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery
has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and
efficacy profiles. This approach involves viral and non-viral delivery systems.
Methods: Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus
and Venezuelan equine encephalitis virus. For immunotherapeutic applications, recombinant particles, RNA
replicons and layered DNA vectors that express tumor-associated antigens (TAAs) and cytokines have been studied
in animal models and in a few clinical trials.
Results: Immunization studies with TAAs and cytokines have elicited strong antibody responses and vaccination
has provided protection against challenges with tumor cells in mouse models. Furthermore, the combination of
TAAs and cytokines, antibodies and growth factors and the co-administration of chemotherapeutics and bacteriabased
adjuvants have enhanced immunogenicity. Intratumoral and systemic delivery of recombinant alphavirus
particles has demonstrated significant tumor regression and prolonged survival rates in rodent tumor models.
Conclusion: Alphavirus-based immunotherapy represents a rapid and efficient method for prophylactic and
therapeutic applications in animal models.
