Reovirus shows potential as therapeutic approach in prostate cancer

MedWire News: Reovirus therapy may provide a promising novel treatment for prostate cancer, researchers report.

Chandini Thirukkumaran (University of Calgary, Alberta, Canada) and colleagues found evidence of in vitro and in vivo activity against prostate cancer, in both preclinical models and six patients with organ-confined prostate cancer.

Writing in the journal Cancer Research, they report that when the human prostate carcinoma cell lines PC-3, LN-CaP, and DU-145 were exposed to replication-competent reovirus, the cells showed evidence of infection as illustrated by viral protein synthesis, cytopathic effect, and release of viral progeny.

Xenograft tumors were transplanted into severe combined immunodeficient/nonobese diabetic (SCID/NOD) mice and these reduced in size after a single intratumoral injection of reovirus.

Immunohistochemical analysis of the major organs of mice treated with live virus revealed reovirus replication within the tumor mass, but not in the brain, kidney, lung, liver, and spleen.

Finally, in a cohort of six patients with clinically organ-confined prostate cancer, intralesional reovirus injections resulted in minimal side effects and evidence of antitumor activity.

Histologic analysis after prostatectomy found a significant CD8 T-cell infiltration within the reovirus-injected areas as well as evidence of increased caspase-3 activity. Five of the six patients showed moderate to strong staining of reovirus proteins in cancer areas, whereas the adjacent benign areas and remote cancerous areas showed negative to weak staining of reovirus.

“This reiterated the fact that reovirus does not seem to infect noncancerous tissue, however, unfortunately, also indicates that reovirus after a local injection likely does not spread to other areas of the prostate cancer in the same patient,” Thirukkumaran et al comment.

The researchers conclude: “The ultimate goal of these investigations is to provide the necessary preclinical data for a full phase I clinical trial in advanced prostate cancer.”

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