Immunotherapeutic Approach for Glioma by Alphaviruses as Positive Strand RNA Viruses

Abstract

Alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of heterologous genes in a wide variety of host cells. The alphavirus vectors, Semliki Forest virus (SFV), Sindbis virus (SIN), and Venezuelan equine encephalitis virus (VEE), have been developed as gene expression vectors. Alphaviruses are positive-strand RNA viruses that can mediate efficient cytoplasmic gene expression in mammalian cells and trigger stress pathways in the cells they infect, culminating in the death of the host. The alphavirus RNA replication machinery has been engineered for high-level heterologous gene expression. Since an RNA virus vector cannot integrate into chromosomal DNA, concerns about cell transformation are reduced. Alphavirus vectors demonstrate promise for safe tumor-killing and tumor-specific immune responses. Recombinant alphavirus RNA replicons may facilitate gene therapy of cancer. This chapter covers the development and applications of alphavirus vectors for glioma immunotherapy.