Replies to post #11577 on NorthWest Biotherapeutics Inc (NWBO)

[Doktornolittle]

"Koman says - I have no idea why choosing multiple tumor injections make any sense at all as the next step.

Perhaps different tumors, although in the same body, express different antigens, and injecting each would cover more possible antigen expressions."

Maybe so. But I would think that most of the time they would be the same animal.

Injecting more than one of them would likely generate a larger systemic response because it would generate more activated DC's and probably involve more lymph nodes.

In addition to the simple linear increase in the systemic response, cluing the body that there are mets might invoke a disproportionate increase in the systemic response as the hunt for mets gets very serious.

It's unknown territory. Testing such possibilities makes sense to me.

And if I were a patient, I would want them to inject every tumor, of course, if they could. But I do understand why they must first check to see if that is even necessary. Just hope that at some point, if the systemic response is not dramatic, that they do follow through with further injections. Even if that had to be at a low dose.

[Pyrrhonian]

Instead, there would be a greater cytokine release, initiating larger immune response. Antigens are same as origin. In metastasis, the understanding is they all basically express the same (unless there are multiple originating tumors--rare).

[koman]

I'm pretty sure that even in one tumor lump, you will find more than one phenotype of tumor cells. Since these patients have gone thru more than one round of treatment, the remaining phenotype of tumor cells are highly resistant to chemo. The most resistant of these phenotype will be the germ/stem cell cd34+ line. the phenotypes become less resistant as they mature and change into differentitated cells. Each of the tumor lumps all started out with one migrating germ/stem cell that metastasized. But the hypothesis is that each lump should be very similar to one another. I'm not sure if the DCVAX Direct individual doses are injected into the same lump each time (which I think is the protocol for now) but I'm wondering if LP is suggesting each time a different lump will be injected. I really don't think it will make much of a difference. But I really wish that NWBO will let someone like Dr. Marnix Bosch to speak since he has a science background. Who is making the decisions in the direction of these trials? I hope it isn't LP.

Also, I sometimes wonder if there was a significant change in the quality of the process used in PI studies by Dr. Linda Liau and the pIII studies in GBM. With personalized treatments, I'd be concerned by the ability to have consistent processes which the pIII trial is utilizing but I'm pretty sure that Dr. Linda Liau used a slightly different process which involved fresher cells and less processing time because there was no need for shipping blood and tissue samples. Will these differences make a significant impact on results? I don't know but the pI results for IMUC and NWBO were both very good, but both were based on one clinical site with a slightly different protocol that had to be altered to adapt to a larger clinical trial with a centralized processing center. One would hope that is not the case, but my first hand experience dealing with blood and isolating stem cells and freezing cells in dmso and cell viability is partly dependent on the handler's skills and time. This may be part of the reason Big Pharma for the most part tries to avoid these type of therapies.