Oncolytic virus therapy is a new method of cancer therapy. Its goal is to selectively target cancer cells sparing healthy cells. However, not many tumors respond to it and so far it has limited application.
So it was interesting to read new study in Cancer Cell that showed that effectiveness of oncolytic virus cancer therapy could be improved by incorporating prostaglandin-inactivating enzyme (hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD).
Initially, the authors tested in vivo susceptibility of several cancer cell lines to oncolytic vaccinia strain (WR.TK-Luc+). Some cancers were less susceptible (Renca, 4T1), some more (LLC, MC38).
Susceptibility to WR.TK-Luc+ therapy was T cell mediated as CD8 T cell depletion could abolish it.
To overcome inhibitory micro-environment within resistant tumors oncolytic virus (OV) expressing prostaglandin-inactivating enzyme was designed. Indeed, modified OV therapy improved cancer protection.
Moreover, when combined with anti-PD1 therapy, modified OV could protect mice from resistant tumor such as Renca tumor, even when applied on established tumor (aspirin had no effect at this stage).
In summary, this study confirms that sustained inactivation of local prostaglandine source could drastically improve anti-cancer effect of OV, especially when combined with checkpoint inhibitors.
David Usharauli
Susceptibility to WR.TK-Luc+ therapy was T cell mediated as CD8 T cell depletion could abolish it.
To overcome inhibitory micro-environment within resistant tumors oncolytic virus (OV) expressing prostaglandin-inactivating enzyme was designed. Indeed, modified OV therapy improved cancer protection.
Moreover, when combined with anti-PD1 therapy, modified OV could protect mice from resistant tumor such as Renca tumor, even when applied on established tumor (aspirin had no effect at this stage).
In summary, this study confirms that sustained inactivation of local prostaglandine source could drastically improve anti-cancer effect of OV, especially when combined with checkpoint inhibitors.
David Usharauli
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