HVJ (hemagglutinating virus of Japan; Sendai virus) was first discovered in Japan in 1950’s. It is mouse parainfluenza virus, not human pathogen. The virus has become very famous since the discovery of virus-mediated cell fusion. Using the fusion activity of HVJ, a versatile drug delivery system, HVJ envelope vector (HVJ-E), was developed.
Recently, we discovered that HVJ-E has anti-tumor activities. One of the activities is enhancing multiple anti-tumor immunities such as activation of dendritic cells, induction of NK cells and CTL, and suppression of regulatory T cells. Another is direct tumor-killing through the induction of type I interferon and cancer cell fusion. Therefore, HVJ-E possesses the properties of both anti-cancer drug and immunotherapeutic reagent. Clinical trial to test the safety and efficacy of HVJ-E has started in 2009. For future therapy, tumor-targeting vector can be developed by modifying fusion protein gene with targeting molecule DNA and knocking out HN protein expression. Single-chain antibodies (scFv) against human melanoma have been isolated by phage-library screening. The tumor-targeting scFV-bound HVJ-E is being constructed. Systemic administration of the tumor-targeting HVJ-E will be achieved in future.
Since HVJ-E has anti-tumor activities such as activation of anti-tumor immunities and direct tumor-killing, the vector itself can be an anti-cancer reagent. Furthermore, HVJ-E was originally developed as a drug delivery vector. Therapeutic molecules incorporated into the vector also enhance the anti-tumor effects. Systemic administration of the tumor-targeting HVJ-E will be achieved in future. Therefore, tumor-targeting HVJ-E containing the therapeutic molecules will be an effective tool to suppress metastasized tumors and tumor-reccurrence.
