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One challenge to using oncolytic viruses as a treatment for cancer is that the viruses may cause off-target effects. I'm curious to know how useful it would be to create an oncolytic virus that has the receptor for another virus encoded into its genome (kind of like a viroreceptor)? It would probably be best if the encoded receptor is a receptor not present in humans, so maybe a receptor present on the surface of another animal's cells. If the first virus replicated to a higher degree in cancer cells than normal cells, and/or if the first virus was largely cleared from the normal cells before the second virus was administered, then it seems the cancer cells would differentially express the receptor for the second virus, and that could limit the off-target effects of the second (perhaps more potent) virus. (Of course, there are other ways of limiting off-target effects - injecting the viruses intratumorally, using viruses that the host would mount a memory response against, etc. - feel free to include these in your answer if you'd like.)

I'm sure there may be challenges in practice (one that comes to mind is whether a given first virus would have the genomic space to carry a receptor for the second, in addition to other desired genes) but I'm curious to know what people about this idea in the spirit of a thought experiment, or if you could point me to any relevant papers etc.

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  • $\begingroup$ From the help center, If your motivation for asking the question is “I would like to participate in a discussion about ______”, then you should not be asking here. In addition, this is an opinion-based question (and thus off-topic) because it is asking about a hypothetical situation. From the help center, avoid asking subjective questions where … you are asking an open-ended, hypothetical question: “What if ______ happened?” We expect answers to be based on verifiable facts and references, along with subject-related expertise. Please see the tour and other help center for details. $\endgroup$ – tyersome May 5 at 21:13
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Short answer: No.

Longer - No. Why would you do this? - if you can get the first virus to replicate to high levels in a manner that is specific to cancer, then why not use that first virus alone rather than run the risk with two separate viruses.

Don't forget that for the virus to reach all parts of the tumour it will need some cell to cell transmission, which means that it exits the cell (possibly in a lytic manner) in the first case, so there probably isn't any need for the second virus.

The second point is that the immune system (innate and adaptive) will recognize the virus infected cells and start to clear them (that's the whole point of oncolytic therapy), probably before the second virus is administered.

Thirdly, not all cell types support viral replication efficiently. This may or may not be the case for the specific virus(es) and cancer types you target, but it is something to be considered.

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