What is the potential of using a modified adenovirus to treat cancer?

[BillTre]

This Science News article reports that researchers using a modified adenovirus (that normally causes mild respiratory infections) that only grows in retinoblastoma tumor cells, researchers were able to improve upon (but apparently not cure) the results of cancer drugs in rabbits and mice. Trials in children (where most cases occur) are beginning.
The modified virus was missing a key gene and could only reproduce inside cells in which the retinoblastoma pathway had malfunctioned.
This is an approach to treating cancer I had not heard about before.

 

[Wrichik Basu]

For the first time, I am hearing that cancer can be treated by a virus. Hope that the method succeeds, because chemotherapy and radiotherapy are way too bad for anyone. On the other hand, it's also pathetic to think of children having their eyeball removed. Can't even imagine it.

One of my close relatives passed away with cancer (not of the eye, but maxillofacial) some years back. Alternatives to chemo and radiotherapy are always welcome if they can produce the desired (or better) results without too many side effects.

If any more news is heard of the success of this method, please let me know. I am interested in this one.

 

[dLouie]

This is a great news if the test results will give positive feedback. Hope there will be no harmful side effects on using a virus as a treatment.

 

[Ygggdrasil]

The idea of treating cancer with viruses that specifically target cancer cells but not normal cells has been discussed for many years. For example, see these previous physics forums discussions on the topic from 2012 and 2015:

https://www.physicsforums.com/threa...biotechnology-and-manipulating-viruss.621459/
https://www.physicsforums.com/threads/cancer-cure-polio.806261/

However, despite the promise of these approaches, progress has been slow in developing these types of viruses and finding ones that are safe and effective in clinical trials. The approach of targeting cancer of the eye is probably the ideal first test case; the inside of the eye is easilly accessible and it is an immunologically privileged compartment, so the virus will not have to combat the body's immune system while it works on the cancer.

Here's a review paper I cited in a previous thread discussing some of the challenges faced by those deveoping oncolytic viruses: http://onlinelibrary.wiley.com/doi/10.1002/cncr.28862/full

the demands on a successful OV platform are enormous. Such viruses must: 1) be categorically nonpathogenic, 2) be genetically stable upon intratumoral replication, 3) target/infect notoriously heterogeneous tumors, 4) elicit efficient killing of infected tumor cells, 5) act in the presence of neutralizing antibodies and innate antiviral immune activation, 6) reverse the immune-repressive tumor/stromal microenvironment, and 7) be capable of recruiting immune effector arms against the tumor target. In addition, there are many unique practical and regulatory aspects to consider, such as 1) particle stability (including within the clinically intended delivery apparatus), 2) reliable and efficient manufacture, and 3) public health implications, eg the availability of protective vaccines/antivirals. Combining these features in a single agent is a tremendous challenge.

 

[LURCH]

the virus will not have to combat the body's immune system while it works on the cancer.

My first thought when I saw this thread was to wonder what kind of side effects do they get from the patient’s immune system when they introduce this virus. Does the isolated compartment of the retina mean that the immune system will not attack at all?

 

[Ygggdrasil]

My first thought when I saw this thread was to wonder what kind of side effects do they get from the patient’s immune system when they introduce this virus. Does the isolated compartment of the retina mean that the immune system will not attack at all?

The inflammatory response is reduced in the eye, but not completely eliminated:
https://www.aao.org/eye-health/tips-prevention/eye-immune-privilege
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948372/

 

[LURCH]

Thank you for those links, biology and medical science are probably my weakest fields. So, the cells within the eye actually have their own immunosuppressants, which they release during an immune response. That is new and very interesting information to me.

I have a little friend who lost an eye to this disease, so I will be following this research with great interest.

 

[Laroxe]

There have been observations of cancers that have suddenly gone into remission following following virus infections for a long time and several natural viruses are clearly associated with anti cancer effects, measles is a good example. As cancers progress they typically mutate and become increasingly unlike their parent cells and an accelerating rate, this can induce a number of changes in the cell metabolism, some of these changes may make them better targets for viruses to infect. The problem is that tumours contain cells with a wide range of mutations so the effectiveness of a virus becomes dependent on the percentage of cells that have the mutations that favour the virus this predicting people who will respond is very difficult and many viruses are highly selective about the types of tumour they are likely to attack. The viruses also have to do their job very quickly as they are recognised by our immune system and neutralised. This has lead to repeated attempts to engineer viruses that don't provoke an immune response and /or with increase their tumour specific effects, but progress has been very slow. However this research has been increasingly linked to other biologic approaches as our knowledge about our immune system improves again we have known that the immune system plays an active role in identifying and destroying abnormal cells, for a cancer to develop it must have evolved strategies to avoid these systems.
When an area of the body becomes infected or damaged our immune system is unregulated becoming more more aggressive and less selective, because this can cause considerable collateral damage our cells use a variety of chemical messengers to control or disable the immune responses, it is often these messenger systems that the cancer cells exploit.
One early observation in virus therapy was that when it worked it clearly had an effect on tumour tissue that had not be specifically infected, the cell death induced by the virus up-regulated the immune response locally, which meant the immune system started killing cells that "might" be infected but it also became better at identifying the features of these cells leading to a systemic effect. While only one oncolytic virus has achieved FDA approval, drugs that manipulate the control of immunity are becoming available very quickly and seem to be changing the whole outlook for cancer, even some of the most difficult to treat are becoming manageable. All of these approaches carry their own risks, often linked to over activation of our immune responses but they are generally far less toxic than traditional chemotherapy but there are still advantages in using combination approaches. This is the start of a new revolution in medicine folks!