NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

I’m certain there will be great interest in Northwest Bio’s DCVax Platform. Not sure if this has been posted, has anyone read the full article?

Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy
Science Translational Medicine  11 Mar 2020

Checkpoint musical chairs
Anti–PD-1 or PD-L1 antibodies can reinvigorate antitumor immunity in a subset of patients with cancer. To better understand the mechanisms behind successful therapy, Mayoux et al. characterized various ligands on the surface of dendritic cells (DCs). PD-L1 on DCs can bind B7.1 on the same cell, potentially preventing PD-1 ligation on T cells or B7.1 ligation of its partner CD28. They saw that PD-L1 was expressed in excess of B7.1, likely preventing T cell stimulation through these two pathways. Patients with a high DC signature before treatment were more likely to respond to PD-L1 blockade. These results reveal that in cis interactions on DCs have immunological and likely clinical consequences for checkpoint blockade therapy.

Abstract
PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity. Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target of PD-L1 blocking antibody. PD-L1 binds two receptors, PD-1 and B7.1 (CD80). PD-L1 is expressed much more abundantly than B7.1 on peripheral and tumor-associated DCs in patients with cancer. Blocking PD-L1 on DCs relieves B7.1 sequestration in cis by PD-L1, which allows the B7.1/CD28 interaction to enhance T cell priming. In line with this, in patients with renal cell carcinoma or non–small cell lung cancer treated with atezolizumab (PD-L1 blockade), a DC gene signature is strongly associated with improved overall survival. These data suggest that PD-L1 blockade reinvigorates DC function to generate potent anticancer T cell immunity.

https://stm.sciencemag.org/content/12/534/eaav7431

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https://stm.sciencemag.org/content/12/534/eaav7431.full