Dear Shalina:

Since NK and CD8+ T cells are the cells most responsible for anti-tumor cellular immunity, I think it would be ill-advised to try something like this.  Chances are very good you'd actually make the tumor more dangerous to the host and allow its rapid metastasis.  I also doubt one could "mask" a functional virion with NK and/or T cell genes.  Did you mean to say gene products, rather than genes?  In any case, I don't see how you could "mask" a virus particle with host-derived molecules and still have it able to interact with its target cells, since its entry into host cells is going to be dependent on viral surface molecules interacting with host cell receptor molecules.

I agree with Joseph. The other issue is that reoviruses are non-enveloped, meaning that they do not have a membrane surrounding them.  Most of the 'masking' proteins that you would want to use would be membrane bound, and thus you cannot express them on the surface of the virus. 

Hello thank you for the responses, I am sorry the question was poorly worded. I agree that reoviruse is non enveloped and masking it wouldn't be correct. I will explain properly as to what I am trying to say.

Reovirus is found to target cancer cells and it can be used as a cancer treatment, but from what I have read in various publications is that in order for this virus to work effectively large amounts is required; since the virus is destroyed by the immune system before reaching the malignant cells. This causes severe side effects to the patients. And I am aware that there have been various approach as to combine chemotherapy and viral therapy but it is not very effective. Similarly the approach of enhancing the patient's immune system has lead to rapid immune responses in many cases, sometimes leading to dead. We know cancer suppresses the patient's immune system, what I am trying to propose is why not combine the reovirus and our immune system cells ( e.g. NK cells) together. The reovirus can be genetically modified to express other genes according to Dr. Rob Hoeben and he has successfully conducted that. If we make the reovirus less immunogenic to the patient's immune system and insert a certain combination of genes from NK cells for example, then the virus can act as the patient's immune system. Various genes in NK cells have been identified to perform various functions. The reovirus and NK cell complex will initiate local immune responses around the malignant cells, this removes the possibility of a rapid immune response in the body.

Basically, I am suggesting is to genetically modify the virus so it works as the patient's immune system and destroys the cancer cells. And since the virus is non pathogenic to humans it will not be harmful. I know the possibility is quite dim and there are many flaws in the idea but it can be developed into something. I hope this makes more sense.

Thanks for the additional information.  I am still a little confused though...

If I understand correctly, you want to use reovirus as an oncolytic virus (cancer killing virus).  The problem is that immune system mounts a very strong response against reovirus, so you can't get enough of the virus to the tumors. 

This is where I get confused, it sounds like you want to genetically modify the virus to express NK cell genes that will act as an adjuvant and enhance the tumor killing effect, is this true?  I have never worked with reoviruses, but it sounds like most patients have a pre-existing immune response that quickly clears the virus, preventing it from reaching the tumor.  Pre-existing immune responses are very hard to overcome.  This has been a paramount challenge in the AAV gene therapy field.  In the AAV field, this is being overcome by mutating the external surface of the virus to allow it to avoid antibody responses.  While theoretically this type of approach might be possible with reovirus, it will probably be challenging (it has taken many years for the AAV field to reach this level of sophistication). 

It is an interesting idea, but are you aware of other work being done using oncolytic viruses?  There are a number of groups working on similar strategies and I'm not sure what the advantage the reovirus system would have over other systems that are more advanced.

If you really want to use reovirus, I would think that using some kind of immune suppression (rituximab or ATG) before giving the virus would allow for it to survive long enough to infect the tumor cells where it can then act.

Good luck!

p.s. while my specialty is gene therapy, I have no experience using oncolytic viruses.

Hello Jonathan, thank you for your response. You understood what I was trying to propose. The only reason I got interested in using the reovirus was because it is non- pathogenic to humans and I have read several papers where the virus has successfully reduced the size of tumors. But this is only achieved if this virus is used in a large amount. There has been quite a lot of work done on this virus and other oncolytic viruses, the main problem that occurs is that the virus is killed my the host immune system. Also, I have read that reovirus has the ability to initiate local immune responses, which can activate the suppressed immune system. I am aware that this approach can be difficult but I don't think its impossible. 

I am glad you took the time to read what I have said. I personally have no background in gene therapy or oncolytic viruses. I am still a 2nd year biochemical engineering student. I just always had a keen interest in cancer treatments and read several articles and thought if we could try this approach could it work or not? 

Just wanted to share my idea thats all thank you for your input. 

Dear Shalini:

I think you fundamentally misunderstand how tumors, immunity and reovirus infections work in intact animals.  An intact mammal isn't an engineering system you can test as one tests an electrical circuit.  

For example, not all reoviruses are nonpathogenic in humans and other mammals.  Even if the reovirus you mention really is nonpathogenic in an intact host (one with intact immunity), tumors survive and spread because they suppress immunity, so your reovirus might prove deadly in a host with suppressed immunity, which any host with a tumor would have (it may interest you to know a defect in immunity is how tumors are often discovered).  Early gene therapy in humans that used viable viruses for vectors  killed some patients even though the virus was considered nonpathogenic, since the frail immune response of these patients allowed nonpathogenic viruses to multiply unabated in the host.