Replies to post #606580 on NorthWest Biotherapeutics Inc (NWBO)

[pgsd]

Thanks for sharing Lykiri. Just the time it takes for the presenter to introduce LL with all of her achievements speaks volumes :-)

[hyperopia]

Thanks Lykiri, not really anything new, but It’s interesting to hear Dr. Liau mention the interferon signature in peripheral blood as a potential biomarker of response to immunotherapy.

And also interesting that Dr. Liau refers to the long term survivor (5+ years) percentage as 20-25% with DCVax, and not the 13% from the clinical trial published results. I think Dr. Ashkan says 30%+.

[hankmanhub]

Thanks Lykiri, that was a grewar tutorial by Prof Liau.

[sentiment_stocks]

Another great video by LL explaining how DCVax-L works, and how it works even more effectively with the CIs and the TLRs like Poly-ICLC.

At a little bit after the 13:50 minute mark, she describes how when the DCs pick up antigens from the dead tumor cells that might be newer (neoantigens?), and we’re not found on the original tumor from which the lysate was made, they could induce a “perpetuated immune response.”

So around the 30 minute point, LL describes in more considerable more detail how the TLRs (Poly ICLC) work with DCVax, thus explaining why the results might be significantly improved by adding this “stimulator” to the immune stimulators.

At the 37 minute mark, she describes an increased “interferon (gama) signature” in the peripheral blood as a potential bio marker to a longer term survival.

Around the 40 minute mark, she talks about a new trial they have planned (based on preclinical mice trials) to go after the immunosuppressive macrophages and myeloid cells that often are battling the T cells by adding a CSF1 inhibitor that is intended to block these immunosuppressive cells.

At about the 51 minute mark, she explains in some detail why the dendritic cell is such a great gatekeeper (or rather communicator) to the immune system alerting it as to what it needs to recognize as a problem.

At around the 57 minut mark, she indicates that the reason why the older patients did so well on DCVax is because their tumors are more mutated and are the made up of the more mesenchymal subtype. So even though a younger patient may have a more robust immune system, their tumors tend to be less mutated. She thinks because the older patients don’t have as strong an immune system, their tumors are more mutated (typically, that’s a much worse scenario); however, those are the types of tumors that immunotherapies do best with.

Anyhow, lots of good stuff in this latest LL video! Thank you! :)

[biosectinvestor]

Thank you so much Lykiri!!! This is a phenomenal presentation by Dr. Liau. They all are very obviously working toward both approval and fully explaining how all of this works to a broader audience.

Happy July 4th to Everyone!!!!

[CrashOverride]

Groundbreaking Trial Data.

[ATLnsider]

Thanks Lykiri, one thing that I am trying to reconcile and understand, is what phase the DCVax-L (ATL-DC) along with poly-ICLC + Pembrolizumab (Keytruda) combination trial is in.

We have seen 2 recent slides that says the combination trial is now in Phase 2, not Phase 1. One slide was presented by Dr. Leia Nghiemphu on 5/19/2023:



Then, on 6/17/2023, Dr. Linda Liau posted this slide that also says this combination trial is also now in Phase 2, and not in Phase 1:



However, on clinicaltrial .gov, it is still showing this trial is still in Phase 1. But, I know sometimes it takes the Sponsor a while to update clinicaltrials. gov:

https://classic.clinicaltrials.gov/ct2/show/NCT04201873

[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.