Efficient eradication of hormone‐resistant human prostate cancers by inactivated Sendai virus particle

Abstract

Hormone-refractory prostate cancer is one of the intractable human cancers in the world. Here, we examined the direct tumorkilling activity of inactivated Sendai virus particle [hemagglutinating virus of Japan envelope (HVJ-E)] through induction of Type I interferon (IFN) in the hormone-resistant human prostate cancer cell lines PC3 and DU145. Preferential binding of HVJ-E to PC3 and DU145 over hormone-sensitive prostate cancer cell and normal prostate epithelium was observed, resulting in a number of fused cells. After HVJ-E treatment, a number of IFNrelated genes were up-regulated, resulting in Type I IFN production in PC3 cells. Then, retinoic acid-inducible gene-I (RIG-I) helicase which activates Type I IFN expression after Sendai virus infection was up-regulated in cancer cells after HVJ-E treatment. Produced IFN-a and -b enhanced caspase 8 expression via Janus kinases/Signal Transducers and Activators of Transcription pathway, activated caspase 3 and induced apoptosis in cancer cells. When HVJ-E was directly injected into a mass of PC3 tumor cells in SCID (severe combined immunodeficiency) mice, a marked reduction in the bulk of each tumor mass was observed and 85% of the mice became tumor-free. Although co-injection of an antiasialo GM1 antibody with HVJ-E into each tumor mass slightly attenuated the tumor suppressive activity of HVJ-E, significant suppression of tumor growth was observed even in the presence of anti-asialo GM1 antibody. This suggests that natural killer cell activation made small contribution to tumor regression following HVJ-E treatment in hormone-resistant prostate cancer model in vivo. Thus, HVJ-E effectively targets hormone-resistant prostate cancer by inducing apoptosis in tumor cells, as well as activating anti-tumor immunity. '

Gene Therapy of Melanoma Using Inactivated Sendai Virus Envelope Vector (HVJ-E) with Intrinsic Anti-Tumor Activities

“…We previously reported that HVJ-E itself has a strong anti-tumor effect against mouse tumors, such as colon carcinoma and renal carcinoma, by the activation of cytotoxic T lymphocytes and natural killer cells and the suppression of regulatory T cells (13,14). Recently, we also determined the direct tumor-killing activity of HVJ-E through the induction of type I interferon on hormone-resistant human prostate cancer cells and human glioblastoma cells (15,16). Thus, HVJ-E is a versatile gene and drug delivery vector with www.intechopen.com Viral Gene Therapy 422 intrinsic anti-cancer activities.…”

A non-replicating oncolytic vector as a novel therapeutic tool against cancer

“…Microarray analysis of genes expressed in PC3 cells after HVJ-E treatment revealed seventeen IFN-induced genes (26) among the twenty most up-regulated genes (25). This result suggests that the secretion of type I IFN (IFN-α, -β) by tumor cells following HVJ-E treatment may stimulate IFN-related genes.…”

“…PC3 cells were intradermally inoculated into the backs of SCID mice, after which each tumor mass was directly injected with HVJ-E on days 10, 13 and 16 after inoculation. In the HVJ-E-treated group, the tumors were completely eradicated in all mice (25). It is known that HVJ-E eradicates mouse renal cancers by activating NK cells (18).…”

“…When the castration-resistant human prostate cancer cells, PC3 and DU145, were treated with various amounts of HVJ-E, the viability of both cell lines was significantly suppressed by HVJ-E in a dose-dependent manner (25). Apoptosis of PC3 cells was clearly detected 24 hr after HVJ-E treatment by Tunel staining of fragmented DNA.…”

Highly Selective Photodynamic Therapy with a Short Drug-Light Interval Using a Cytotoxic Photosensitizer Porphyrus Envelope for Drug-Resistant Prostate Cancer Cells

“…HVJ-E has two characteristics suitable as a carrier of the PS to drug-resistant prostate cancer cells. First, receptors of HN protein are more expressed in human drug-resistant prostate cancer cell lines PC-3 and DU145 compared with the normal prostate epithelial cell line PNT2 [17]. This cancer-specific expression of receptors enables HVJ-E to selectively deliver the PS to such prostate cancer cells.…”