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etienne555

01/07/14 6:26 AM

#3224 RE: etienne555 #3222

The results for the first few patients treated by Direct will surely give us a glimpse to what to expect.

I wasn't very clear in another post about a tumour being injected and then removed! It seems to me that direct is better than L, but still it is to early to make such assumption, and anyway maybe we cannot compare inoperable and operable. But Flipp wrote in the past about antigen from dead/live tumor... in vivo /ex vivo, I will reread more about it. Just hope L is very efficient.

flipper44

01/07/14 11:00 AM

#3227 RE: etienne555 #3222

I've slightly updated my thinking on the difference.

Direct is likely better because:

1. Intratumoral dendritic injections have proven superior.
2. DCVax-Direct is/are dendritic cells matured to their most effective state -- partial maturation.
3. DCVax-Direct is stimulated to become the most effective type -- identified by cd40 expression and il-12 production.
4. Sometimes its ok if the king wears no clothes (like when he's taking a shower)….In other words, its no secret ultimately DCVax Direct -- if proven very successful -- will be used on operable as well as inoperable tumors.
5. DCVax direct is loaded with antigens from dying (but not dead) tumors. This is where I am updating my explanation. Thus far it appears that a dying/weakened tumor is even better at presenting antigens/biomarkers to DCVax-Direct than a healthy or dead tumor is.
6. It does not require surgery, tumor preservation and processing.


The benefits of numbers 1,2 and 3 above make the dendritic cells better at:

a. Going directly to the antigen source of a dying tumor.
b. Responding better to the immunosuppressive environment the tumor immediately throws at it.
c. Taking up antigens and biomarkers in their most relevant states.
d. Orienting and mobilizing DCs back to the lymph nodes.
e. Expressing their antigens/biomarkers to the natural killer t-cells, b-cells (which make antibodies) and helper t-cells more effectively because dendritic cells perfected in stages 1,2 and 3 above were not down regulated by the otherwise immunosuppressive environment of the tumor.


On the other hand, L is first partially matured outside the body, then fully matured outside the body with grounded up tumor lysate. It is unlikely NWBO was able to modify the L partial maturation process in-between phases 1/2 and 3 to otherwise reflect the superior dendritic cell maturation (used in direct) to (a more) correct stage and type. This is because the learning and benefits put into DCVAX-Direct were only really known after the first phase of the L trial began. It is unlikely L was allowed to further improve its product after the trial started, but I am not certain about this. Further, L is not injected into the tumor bed, and as you know, uses dead -- not dying -- tumor lysate. I could explain those things in more detail, but I think you get what I'm trying to say.

The eventual outcome will tell the real story, and we will see what transpires.

P.S. Of course, I still think that DCVax-L will prove superior to any non-DCVax platform.