Replies to post #156525 on NorthWest Biotherapeutics Inc (NWBO)

[marzan]

Thanks flipper for explaining to us the difference. Are both of these agents chemos flipper? I see they need a prior tumor infiltration for the T cells to amplify with that tumor specific protein. But if the tumor load is so huge that the protein is not there already done consumed fighting, then this technique may not work, right?

[jondoeuk]

CpG can target either plasmacytoid dendritic cells and/or B-cells (depending on the class). The former (immature) are recruited to a tumour and then are converted to help maintain tolerance/suppression http://onlinelibrary.wiley.com/doi/10.1189/jlb.0812397/full

Intratumoral injections of one drug (FLT3L) http://www.cell.com/cancer-cell/fulltext/S1535-6108(14)00370-5 http://www.cell.com/immunity/fulltext/S1074-7613(16)30101-7 could help increase certain DC subsets and then these could be targeted with different TLR agonists https://jitc.biomedcentral.com/articles/10.1186/2051-1426-2-12

Or you could combine CpG with a range of mAb's and inject them all into the tumour https://www.jci.org/articles/view/64859

[sentiment_stocks]

Maybe I’m missing something here. While it’s always good news when something is found to eliminate cancer - I think more questions need to be answered before one considers this could be the same as or better than DCVax-Direct. I know that’s NOT what you are implying by your post flipper - I’m merely responding to your post as I would imagine you (and several others) may have more insight into this treatment than others.

I think it would be important to know exactly what proteins is this approach targeting when it’s injected into the tumor?

Was it a B-cell lymphoma tumors that these two agents (CpG oligonucleotide and and some unidentified antibody that binds of OX40) were targeting?

Or was it T-cell lymphoma (15% of all lymphomas)? Or another type?

How many proteins or antibodies was this approach going after?

Do lymphoma cancer cells usually just have a few, or are they characterized by having many?

The CAR-Ts that have so-far been approved have gone after the B-cell lymphomas when no other treatment will work for them. There are plenty of lymphoma cases that can utilize other treatments and they will be effective for them. For the rare few that have gone that route and it’s not worked… CAR-Ts may be their only option. And we know that these CAR-Ts thus far have been shown to be successful in some cases to eliminate these B-cell cancers in these types of patients with no other options left (if it doesn’t kill them first).

But it has also been pointed out that CAR-Ts also eliminate all the B-cells in the person as well.

So… targeting one antigen or protein and getting rid of it is a good thing. The problem is, though, that if there are other targets on the cancer that the treatment doesn’t target, what good is that? This treatment described in the Stanford article didn’t appear to have any effect at all in the colon cancer cell line, just the lymphoma cancer. Is this treatment similar to rindopepimut for GBM that could eliminate EGFRv3 but did not do anything to prevent the GBM from returning because there were still plenty of other targets on the cancer?

Scientists can state things as they did in this article like,

“I don’t think there’s a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system.”

which sounds really great.

But really, how accurate is that? They are talking about a test they did with mice on what may be just one or two targets on a lymphocyte tumor. As we know, DCVax-Direct is designed to target everything on the tumor. And of course, the side effects are negligible.

So IMO, these are things that need to be considered and answered before one can really begin to consider that this type of treatment may be right behind DCVax-Direct in the treatment of inoperable solid tumor cancer.

Do you see my point flipper (or others) or am I missing something?