NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

Hi Doc Logic,

Did you notice that he has been using the first Phase I trial as his example of what he calls poor survival? We are talking pre-STUPP protocol. There was no concurrent chemotherapy with radiation. Temozolomide had not even been approved as the standard of care at that point. It was used as an adjuvant after vaccine. Patients received a maximum of 3 vaccine injections in that trial. And surgical care use of FGS or iMRI came after those patients were enrolled. I think he added significant negative bias to Linda Liau's paper and framed it improperly, out of context. Bulky tumors were common then. Gross total resection rates were not what they are today. Second surgeries are not what they are today. At the time that initial Phase I study ran the standard of care (surgery and RT) had patients living significantly shorter than then current protocols. Here is the paper. Folks should read it for themselves.

Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local Central Nervous SystemTumor Microenvironment

Linda M. Liau,1,5,6 Robert M. Prins,1Sylvia M. Kiertscher,2,6 Sylvia K. Odesa,1 Thomas J. Kremen,1 Adrian J. Giovannone,1 Jia-Wei Lin,1 Dennis J. Chute,3 Paul S. Mischel,3,5,6 Timothy F. Cloughesy,4,5,6 and Michael D. Roth2,6

Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulateTcell ^ mediated antitumor immune responses against brain tumors in ani- mal models. As a next step in vaccine development, a phase I clinical trial was established to eval- uate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme.

Experimental Design: Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 Ag per injection) of acid-eluted autologous tumor peptides. All patients had histologically proven glioblastoma multiforme.Three biweekly intradermal vaccinations were given; and patients were monitored for adverse events, survival, and immune responses. The follow-up period for this trial was almost 5 years.

Results: Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic anti-tumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor h2 (TGF-h2). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight
patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated withTGF-h2 expression within the tumors and positively correlated with clinical survival (P = 0.047).

Conclusions:Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with lowTGF-h2 expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell ^ based vaccines.

http://www.aimath.org/WWN/tumorimmune/LiauDendriticCellVaccination.pdf


Just for the record, Liau and Prins release the 2015 abstract both in the US and in the EU; slight variations, same 14.7 Median Survival for recurrent patients conclusion. :)