NorthWest Biotherapeutics Inc (NWBO)

[Evaluate]

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI
Joseph P. Antoniosa,1, Horacio Sotoa,1, Richard G. Eversona, Diana L. Moughona
, Anthony C. Wanga, Joey Orpillaa, Caius Radub,c,d, Benjamin M. Ellingsonc,e, Jason T. Leeb,d, Timothy Cloughesyc,f, Michael E. Phelpsb,c,d,2, Johannes Czerninb,c,d, Linda M. Liaua,c,g, and Robert M. Prinsa,b,c,g,
2017

http://www.pnas.org/content/pnas/early/2017/08/30/1706689114.full.pdf?with-ds=yes

Significance
The inability to accurately monitor glioblastoma tumor progression
vs. pseudoprogression has severely limited clinical
treatment decisions, especially in the setting of immunotherapy.
We have identified a novel noninvasive imaging combination
that could distinguish intracranial immune responses
from tumor progression in mice bearing orthotopic gliomas
and in patients with glioblastomas. We combined the use of
advanced MRI with PET imaging of deoxycytidine kinase, an
enzyme overexpressed in immune cells. This combination
resulted in superior differentiation between immune responses
and tumors within the brain, and identified peripheral lymph
nodes in which immune responses occurred after immunotherapy
combinations.
This combined imaging approach may
provide a useful method to clinically monitor patients with
glioblastomas treated with immune-based therapies, and to
distinguish tumor progression from pseudoprogression.

In an ongoing imaging study, we performed [18F]-CFA PET imaging on patients with recurrent GBM before and after two immunotherapeutic treatments consisting of autologous tumor lysate-pulsed DC vaccination (DCVax-L; Northwest Biotherapeutics) with or
without PD-1 mAb blockade (pembrolizumab; Merck).
The case studies of the first three patients are outlined below.

Patient C (not pictured) had a recurrent frontal tumor that was treated with bevacizumab and DC vaccination, which resulted in a complete objective response. Because of this, there was no evidence of disease to quantify by imaging at the time points studied

Fig 4 regarding overall survival is also interesting.

Over the past decade, experimental immunotherapeutic trials have been hindered by the lack of reliable and systematic measures of immune responses within central nervous system (CNS) tumors. In our preclinical models of glioma, the activated tumor infiltrating T lymphocyte response is responsible for extended survival and therapeutic benefit (1, 23). DC vaccination alone is able to promote an infiltrating T lymphocytic response, but the addition of PD-1 mAb conveys a significant survival benefit only when combined with DC vaccination