Immunostimulatory virotherapy using recombinant sendai virus as a new cancer therapeutic regimen

Abstract

The utility of recombinant Sendai virus (rSeV) has been considerably examined over the last decade as a potent gene transfer candidate in a cytoplasmic gene expression system. Such risks as excessive immune responses associated with this virus administration in vivo however have limited its applicability in clinical settings as is the case with other viral vectors including adenoviruses. In consequence of extensive assessment on the mechanisms of immune responses against SeV, we found that ex vivo infection of immature dendritic cells (DCs) with SeV demonstrates their spontaneous maturation and activation. We applied this result to create a unique, representative, and powerful agent to activate DCs, namely rSeV-modified DCs (rSeV/DCs), for use in cancer immunotherapy. Use of this system in vivo resulted in the induction of efficient antitumor immunity against vascularized rodent tumors, including melanoma, hepatocellular carcinoma, neuroblastoma, squamous cell carcinoma, and prostatic cancer, and it even frequently associated with elimination of those tumors. These results indicate that rSeV could be a powerful immune booster for DC-based cancer immunotherapy that is worth investigating further. We propose a conceptual term "immunostimulatory virotherapy" to describe this new method of cancer therapy using the rSeV/DCs system.