NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

Thanks Senti!

Also, last night I posted this on Twitter.

1/ Re $NWBO and #DCVaxL aka "ATL-DC" in brief:#DrLindaLiau, principal investigator for a Phase 3 #DCVaxL trial recently gave a lecture covering the #DCVaxLComboTrial with #Keytruda.

— biosectinvestor (@biosectinvestor) April 20, 2022

I included this screen shot from Dr. Liau's March 31, 2022 presentation at University of Miami:



With the further explanation:

"In reference to the combination, the slide clearly states at the bottom of the boxed section, "Induction (DCVax) of T cell response + inhibition of PD-1/PD-L1 interactions (anti-PD-1) leads to TIM upregulation"."

The Danish Dude further added a link in another thread later, which is more official:

https://trp.cancer.gov/spores/abstracts/ucla_brain.htm#h03

Project 1: Active immunotherapy combined with checkpoint modulation for glioblastoma

Project Co-Leaders:
Robert M. Prins, PhD (Basic Co-Leader)
Linda M. Liau, MD, PhD, MBA (Clinical Co-Leader)

The overall goals of this research project are to investigate mechanisms of immune evasion following treatment with dendritic cell (DC) vaccines, and to develop rational combinations of immunotherapeutic strategies to overcome the immunosuppressive milieu of the brain tumor microenvironment. Our previous work strongly suggested that, in addition to inducing T-cell infiltration into brain tumors, DC vaccination may also create a pro-inflammatory environment within the tumor that induces the immigration of immunoregulatory antigen presenting cells (defined herein as iAPC) expressing high levels of PD-L1 and IL-10. These cells are phenotypically similar to the iAPC that dominantly attenuate the T-cell response to chronic viral infection, and may counteract the effective anti-tumor T-cell responses induced by DC vaccination within the tumor microenvironment via a mechanism involving PD-L1/PD-1. Furthermore, inhibition of iAPC using an anti-PD-1 mAb or a CNS-penetrant CSF-1R inhibitor (PLX-3397) in conjunction with tumor lysate-pulsed DC vaccination (DCVax-L), resulted in significantly prolonged survival in tumor-bearing animals with large, well-established intracranial (i.c.) gliomas. We therefore postulated that clinically relevant anti-tumor cellular immunity against GBM must have two components: 1) significant induction of tumor-specific tumor-infiltrating lymphocytes (TIL); and 2) blockade of iAPC function within the tumor microenvironment. Our hypothesis is that the local cellular interactions between iAPC and T lymphocytes within the tumor microenvironment will be a critical factor influencing the efficacy of immunotherapies in glioblastoma patients. A better understanding of the biology of these cells should provide insight into more effective ways to induce therapeutic anti-tumor immune responses for this deadly type of brain tumor.

The three Specific Aims of this project are:

Aim 1: To understand the mechanisms by which iAPCs limit glioma-specific anti-tumor immune responses induced by active immunotherapy

Aim 2: To evaluate the efficacy of combining tumor lysate-pulsed DC vaccination (to induce TILs into the tumor) with immune checkpoint inhibition (to block iAPC function) in pre-clinical models in vivo, and explore the use of novel PET tracers as an imaging biomarker of response.

Aim 3: To develop predictive immunological and imaging biomarkers of response in recurrent glioblastoma patients enrolled in a Phase II clinical trial of DCVax-L +/- Nivolumab.

Proposed schematic of how non-neoplastic cells can be effectively targeted to influence clinically relevant anti-tumor immunity and immunotherapy

The importance of PD-1/PD-L1 in iAPC-mediated immune suppression. Proposed schematic of how non-neoplastic cells can be effectively targeted to influence clinically relevant anti-tumor immunity and immunotherapy

Yup, you're right.

The combo trial with Keytruda and the text mentions DCVax-L

SPECIFICALLY

Game over mr. Feuerstein!https://t.co/Nh58M3BBLs pic.twitter.com/SdrJP88yBE

— 🇩🇰 The Danish Dude 🇬🇱 (@FlemmingBruce) April 20, 2022