NorthWest Biotherapeutics Inc (NWBO)

[Chiugray]

Lykiri, That’s a great presentation by Linda Liau. It is about her scientific journey coming up with what we all talk about so much here: DCVax-L + CI + Poly ICLC + CSF1R inhibitor.

Here’s my brief summary.
1. DCVax activates T cells to fight the cancer tumor. It is very effective but the effect is mitigated somewhat by a tumor defense. The tumor sends out PD-L1 proteins to attach to the T cell’s PD-1 receptor. When activated, this is a checkpoint that down-regulates the T cell.

2. So, a PD-1 inhibitor, aka checkpoint inhibitor (CI), neo-adjuvant drug was added. It is very effective in fighting this tumor’s defense.

3. But something interesting, our immune system has a delicate check-and-balance that prevents the immune system (T cells) from acting too strongly or proliferating in a too big a way, as to inadvertently attack “self”, ie autoimmune response. The check is, it needs a certification in the existence of a pathogen or in this case cancer. Only then will it will send out a “danger signal”.

That certification and danger signal is performed by Toll-like Receptors (TLR) and is done by releasing cytokines (IL-12, IL-18) telling the immune system to ramp up. What stimulates TLRs? The Poly ICLC compound does.

4. So, Poly ICLC was added as an immuno-stimulating adjuvant.

But the tumor has a second defense. In the face of a massive T cell response and CI's that shuts down its first defense, it finds a way to get immunosuppressive macrophages and myeloid suppressor cells to flood the tumor environment and down-regulate the immune response again. So what is known to block this type of immunosuppression? CSF-1 inhibitors.

5. So, a cytokine, CSF-1 inhibitor was added.

This is a nice insight into the mindset of continual therapeutic optimization in the fight against cancer.