Covid Vaccine vs. GBM

[Harvey]

Hello Al,

based on theoretical analysis (and first experiences -if available), which Covid vaccine technology would you prefer for GBM patients? One with mRNA technology (Moderna, Biontech) or modified adenoviruses as a carrier virus (AstraZeneca) ?

I’ve read somewhere that mRNA modified viruses tend to home to tumors..and therefore, theoretically, they wouldn’t produce sufficient COvid protection, but on the other hand, it is possible that the mRNA vaccine makes GBM immunologically speaking „hot“ and produce an immune response?

Thanks,
Harvey

[netopolis]

I'd like to answer this, hope that's OK.

Without reading any related papers, I'd say such effects of Covid vaccines would be highly unlikely. Even if mRNA vaccine was injected directly into the tumor site it would be hard to deliver those nanoparticles to tumor cells only and throughout the tumor tissue (even with convection-enhanced delivery or ultrasound which may damage the nanolipid carrier or ssRNA, a delicate molecule).

Covid mRNA vaccines encode for highly virus-specific antigens which are then presented to the immune system so there is no reason I can see for those vaccines to affect gliomas at all.

If some of the tumor cells were infected by SARS-CoV-2 they would likely be killed off by virus replication induced lysis with or without the vaccine. This would make some tumor cells lysate which could, again in theory, induce some immune reaction but you probably wouldn't want a too strong immune reaction in the brain since the virus is probably not discriminating between tumor and non-tumor cell (unless gliomas express much more certain kinds of receptors which I won't go into for sake of brevity).

The vaccine should probably prevent getting those cells infected in the first place which means no virus-induced tumor lysate in the brain.

Radiotherapy and surgery also create tumor lysate, obviously that's not enough to induce a strong immune reaction against gliomas.

Even much more sophisticated viral therapies have failed to produce significant benefits for most patients in advanced trials. Those that did, produce good results only in a subset of patients. Unfortunately, it's still not known how to identify responder subpopulations.

Primary brain tumor microenvironment is also a problem since it's highly immunosuppressive and adds a lot to the tumor being "cold" in addition to the theory that gliomas don't present enough tumor-specific antigens.

All of this is not saying that glioma therapies could not be made on a similar platform (nanolipid encapsulated nucleic acids) but if we want action against the tumor then those nucleic acids should encode for other kinds of proteins.

I like the approach of Toca 511 & Toca FC (which failed to meet its primary endpoint but leaving a tail of responders and long-term survivors) and the idea of "armed viruses" from DNAtrix which still have a long way to go.

Oncolytic virotherapy is a very promising field since viruses can be made to target only or mostly cancer cells and both deliver different kinds of genes inside those cells and cause an immune response.
IMO, in the future, such therapies should use viruses as vectors to inject multiple genes encoding for proteins that fight tumors in more than one way to have better efficacy and more responders.

Lastly, none of the vaccines you mentioned are "mRNA modified viruses". First 2 are not even viruses.

Wish I could give a more optimistic view. We all need an effective therapy or combination of therapies as soon as possible, or at least something to extend our lives.

Please comment or correct me if you find any misinformation.

[musella]

Netopolis - of course you are always welcome to comment! We need more discussions like this here!


I am not a vaccine expert... but I agree with what Netopolis says. I doubt that the tumor is going to be affected at all, so it doesn't matter which vaccine is used.
However, the technology used in the mRNA vaccines should be simple to modify to our needs to fight the brain tumor. We just need to find the right combination of targets, load it up into the vaccine and try it.