Interesting.
Below is my ham and egg interpretation of what is going on in that study. It sounds like I am certain, but its simply my humble opinion.
This was one of those studies that had a little bit of DCVax-L, DCVax-Direct and something completely different.
I am not surprised by the OS lengthening while PFS was standard.
Why?
First and foremost, these were intranodal injections. That means the Dendritic cells were injected into the lymph nodes (which the brain proper does not have, so Yang had to use cervical and nasal associated lymphs), and not the tumor (as in Direct) or the arm (as in L). This would likely account for the standard PFS response in comparison with historical TMZ/radiation therapy, but longer OS (in comparison to chemo/radiation alone but not longer than DCVAX-L phase 1/2).
In other words, dendritic cells don't just do their job (uptake and expression) in the lymph nodes, they also can and will do them directly in the tumor. When you inject intranodally, you reduce the opportunity for local Dendritic - T-Cell/B-cell/Helper T-cell exchange at the tumor site. Consequently, you reduce the chances of immediate interference with tumor progress (PFS), but you still have the opportunity for longer term interference with tumor progress (thus improving OS, but not to the level of DCVAX-L or DCVAX-Direct). When you inject into the blood stream (as in DCVAX-L), you increase the opportunity for both tumor and lymph dendritic cell exchanges with T-cells/B-cells/Helper T-cells. When you inject intratumorally (as in Direct), you highly increase the opportunity for dendritic cells to exchange with T-cells/B-cells/Helper T-cells in the tumor and the lymph nodes.
Think of it like the dendritic cells, T-cells, B-cells, helper T-cells being placed down stream in the lymph nodes and having to swim upstream (which the dendritic cells are not really meant to be good at), versus them being placed upstream in the tumor (like direct) or easily shuttled to the tumor from the bloodstream (like L). The trip for dendritic cells, to start up stream then move down stream, is much more natural. Dendritic cells are all over the body (especially in the blood), but their primary action with a tumor is to go there first, nibble, mature and then either stay put and express and/or move to the lymphs to express. (Note: ICT-107 was injected subdermally, thus like L, it has a more profound affect on PFS than an intranodal injection).
Second, the tumor lysate in this experiment only selected for IL-12 expression on the matured Dendritic cells (Direct selects for IL-12 and CD-40).
3rd, the stage of the dendritic cell was unclear, but appeared to be fully matured (not partially matured as in Direct).
As Linda Liau stated in her 2010 review, the place where the dendritic cells are introduced is extremely important. Subdermal and particularly intratumoral seem to have the best affect.
