Replies to post #34061 on NorthWest Biotherapeutics Inc (NWBO)

[koman]

Quote "Sounds pretty similar to Direct (including immature DCs) "

Let's just say that this grp's treatment using intratumoral DC vaccine is far more advanced with better chance of success than DIRECT. IF DIRECT could only show something similar to this Japanese grp's study results, then I would have hope that DIRECT works. They did a much better job designing a trial that addresses tumor burden, tumor microenvironment, adjuvant, and other factors to give the intratumoral DC injection a better chance of promoting a stronger immune response.

http://www.hitvlab.com/images/publications/Dr_Hasumi_HITV_Cancer_Journal_Article_April_2011.pdf
5. Conclusions
In summary, combining immunotherapy with radiation was shown to successfully eliminate
metastatic and recurrent tumors on initial treatment in 21 of 26 patients with 13 of the 26 having no
evidence of recurrent disease when evaluated by CT (or PET-CT) at various intervals of follow-up.
The overall disease-free interval of the responding patients at the current time is 377 days. This
remarkable response supports the concept that combinations of conventional anti-cancer therapies and
cancer immunotherapy are worthy of investigation in patients with advanced cancers as well as in
patients that are undergoing primary adjunctive therapy for their disease.

[flipper44]

Fascinating find f3tt3f. The response difference Hasumi obtained treating small lesions and/or a small number of lesions (x<5), is exceedingly better than the result Hasumi received in patients with larger lesions and/or lesions numbering over 5. Thus HitV's therapy does not appear to demonstrate a strong systemic effect:

One year following the last cycle of treatment, among 37 patients initially presenting with recurrent or stage IV disease and bearing = 5 neoplastic lesions that were = 3 cm in diameter, 23 exhibited a CR (62.2%), 5 manifested a PR (13.5%), 2 had stable disease (SD, 5.4%) and 7 displayed progressive disease (PD; 18.9%). Among 74 patients with larger and more numerous tumors who presented with recurrent disease, 7 exhibited a CR (9.4%), 3 displayed a PR (4.1%), 2 had SD (2.7%) and 62 (83.8%) had progressed. Finally, among 56 patients that presented with stage IV disease and large tumor burden, 2 were found to exhibit a CR (3.6%)2, 2 manifested a PR (3.6%) and the remaining 52 exhibited PD (92.9%). --http://www.hitvlab.com/images/publications/Hasumi_OncoImmunology_Oct_2013.pdf

It's interesting, I was just recently speculating on short term low dose radiation combined with DCVax.

One thing to remember is the phase I/II DCVax-Direct trial is using partially matured dendritic cells in inoperable tumors. They are not utilizing radiation in this phase I/II. Even so, the very little information we received thus far on DCVax-Direct with only one tumor injected at each procedure during a very conservative dosing regimen is that they are seeing tumor infiltration levels nearly equivalent to the best responding group results above (group 1). It's far too early to know how this translates, without further DCVax-Direct data. Nonetheless, as we now are entering the time when multiple tumors are and/or will be injected in the phase II portion of the phase I/II Direct trial, at optimum dose, frequency and maturity, we may expect the partially matured (not immature as in the above trial) to show what they can do.

I would think the main limitation in the Hasumi trial is the inability to get consistent responses beyond the tumors and tumor areas that were irradiated and injected. I speculate this may have to do with the maturation level and other factors related to the dendritic cells they used.

Still, very encouraging.