NorthWest Biotherapeutics Inc (NWBO)

[ae kusterer]

hyperopia
Re: ATLnsider post# 692493
Sunday, May 19, 2024 2:00:26 PM

Right ATLnsider, as you indicate, in the UCLA combination studies with DCVax-L, the poly-ICLC is administered separately as an adjuvant. However, in the early studies with DCVax-Direct, it was used in the manufacturing process, which increased the potency. (poly I:C, or its derivative, poly-ICLC is included in the Direct patents, and the more recent hyperactive patents)

NW Bio Receives U.S. Patent On Broad Processes For Producing More Potent Dendritic Cells
Next Generation Technology Already In DCVax®-Direct; Will Be Applicable To All DCVax® Products

Building upon the pure immature dendritic cells, NW Bio's patented methods develop mature and activated dendritic cells that are far more potent than dendritic cells produced in the standard way. For example, NW Bio's dendritic cells produce as much as 10X or more the amount of signaling compounds which are key to mobilizing other active agents of the immune system, such as T cells (which infiltrate and attack tumors) and B cells (which produce antibodies).

NW Bio is already using these next generation methods for producing more potent dendritic cells in its production of DCVax-Direct. The same patented methods for activating dendritic cells were also used in the pre-clinical animal studies with DCVax-Direct. In those studies, injection of these potent dendritic cells into some of the tumors in each of the animals resulted in complete clearance of all tumors (both the tumors injected with DCVax-Direct and the tumors not injected) in 80-100% of the animals in the various studies, indicating a system-wide immune response.
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Going forward, NW Bio's now patented methods of producing more potent dendritic cells will also enable development of the next generation of NW Bio's other two product lines: DCVax-L and DCVax-Prostate. The current DCVax-L and DCVax-Prostate products have already delivered striking results in clinical trials to date, extending the time to tumor recurrence and the patients' survival time by 1-1/2 to 2 years or more, with a substantial portion of patients going far beyond that. Incorporating NW Bio's patented methods for more potent dendritic cells will enable production of enhanced versions of these DCVax-L and DCVax-Prostate products.

https://www.prnewswire.com/news-releases/nw-bio-receives-us-patent-on-broad-processes-for-producing-more-potent-dendritic-cells-198760831.html


For DCVax-L, Northwest Bio uses the most common method of culturing PBMC’s to generate dendritic cells, which relies on the monocytes adhering to the bottom surface of the polystyrene culture vessel in a medium of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), which induces differentiation into dendritic cells, and activates them.

I believe this increased-potency knowledge was gained in the DCVax-Direct studies because they were attempting to overcome the tumor’s defenses by delaying the activation and maturation of the dendritic cells, which wasn’t possible using culture flasks that are used to produce DCVax-L, so they attempted culturing the monocytes in suspension, in a bagged system without IL-4, using only GM-CSF, and then various other mediums to optimize and activate the dendritic cells, including poly I:C.

Northwest Bio stated that they intended to use this higher potency method across all product lines for the next generation of DCVax, but the Flaskworks’ eden system uses a polystyrene culture cartridge (similar to the well plates used in manual culturing protocols) which the monocytes adhere to, so I’ve not seen evidence that they’ve actually changed the manufacturing method for the next generation of DCVax-L. I believe the method of combining poly-ICLC with DCVax-L requires separate (nearly simultaneous) injections to produce the more potent effect in vivo.




ATLnsider

Re: hyperopia post# 692015

Thursday, May 16, 2024 6:26:39 PM

hyperopia, I noticed that you referenced me in this post.

ATLnsider has speculated that Northwest Bio is using poly-ICLC as a maturation and activation agent in the manufacturing process of DCVax-L and therefore, thinks it will be included in the marketing application. While I believe this manufacturing method may have been studied, I believe it was with DCVax-Direct, and not DCVax-L.


I wanted to correct and clarify my beliefs about DCVax-L and poly-ICLC. Here are my beliefs and opinions:

(1) I do not know for sure if poly-ICLC was included in the MAA filed with the MHRA.

(2) I hope poly-ICLC was included in the MAA filed with the MHRA, because more cancer patients will live longer, and more cancer patients will be effectively cured (5 of more years overall survival).

(3) After the 2010 clinical trial at UCLA proved that poly-ICLC was the best TLR agonist to use with DCVax-L (sometime around 2014), all current and future DCVax-L clinical trials have included DCVax-L along with poly-ICLC as the new control. There are no current clinical trials or future planned clinical trials, that do not include DCVax-L along with poly-ICLC.

(4) I am not aware of any clinical trials that have studied poly-ICLC with DCVax Direct. All of the completed trials, and future planned trials that I am aware of, are with DCVax-L along with poly-ICLC.

(5) The recently published peer-reviewed Nature study was of DCVax-L (ATL-DC) along with poly-ICLC.

However, I do believe there will be future basket trials with DCVax-L and DCVax Direct, along with poly-ICLC, that will test the efficacy and safety in treating multiple solid tumor cancers.