Understanding the logistics of oncolytic virotherapy

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The discussion centers on a paper examining the use of an oncolytic poxvirus to deliver membrane-bound Fas ligand to induce apoptosis in normal cells while allowing viral replication in FasR-negative cancer cells. The authors propose that this mechanism will selectively target cancer cells, as normal cells expressing FasR will undergo apoptosis, halting viral replication. However, there is confusion regarding how this approach will prevent productive replication in normal cells, given that the Fas ligand could induce apoptosis in adjacent normal cells. Concerns are raised about the potential for the virus to enter the bloodstream and affect other normal cells, complicating the efficacy of the treatment. The discussion highlights the challenge of ensuring that the virus targets cancer cells, which typically have higher metabolic demands, while avoiding harm to healthy tissues. Modifications to the virus for better targeting of cancer-specific receptors are suggested, though their effectiveness in live patients remains uncertain.
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I have questions about a particular paper: Oncolytic Poxvirus Armed with Fas Ligand Leads to Induction of Cellular Fas Receptor and Selective Viral Replication in FasR Negative Cancer

The authors explain that they're using an oncolytic virus to deliver membrane-bound Fas ligand to cells in a non-specific manner. Their hypothesis is that apoptosis will be induced in normal cells which are FasR+, thereby aborting viral replication, whereas in cancer cells that have knocked out FasR, the virus will replicate fully and lyse the cell.

I'm confused as to how inducing apoptosis in this way will lead to abortive replication in normal cells. If FasL is membrane-bound, won't the virus-infected cell expressing it induce apoptosis in an adjacent, normal cell? That doesn't really seem efficacious.

Am I incorrect in assuming that somewhere along the line, there will be a normal cell that allows for productive replication of the virus?
 
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yeah that's the problem if you inject a vial of fluid of virus that might enter the blood stream and go to other places. The idea that favors anti cancer is that cancer cells usually have a higher metabolic requirement which will become the target of most of the virus. You can always modify the virus to bind with unique cancer receptors, but who knows how well that will go on a live person.
 
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