NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Agreed. Long and I also posted on this matter recently. Thanks. It is very important.

See posts 19202 and 19206. Or read below.

Flipper said:

Early signs of possible systemic effect are: tumor load (numbers) stabilized and/or went down in patients furthest along in the trial, at least one or two patients appear to have achieved some level of remission.9 of 9 of the earliest dosed patients responded and apparently are still alive. T and B cell tumor infiltration . IMHO.

Tumor infiltration with t and b cells in the UCLA phase II Direct study and MD Anderson phase I Direct study demonstrate the injected cells are making it to the lymph nodes, and the t and b cells are targeting tumors, and apparently they are not just targeting the bacterium antigens, but they are targeting the actual tumor antigens as well.

As I stated before, Dendritic cells work in phases. The first phase, which remains ongoing, occurs right after the dendritic cell is injected into the tumor. This is when the DC secretes massive amounts of cytokine that directly and indirectly kill the tumor and create inflammation. The dendritic cell can then uptake tumor debris/antigens/biomarkers/proteins and express them to T and B cells back at the lymph nodes and spleen. The second wave of tumor killing occurs when these T and B cells infiltrate the tumor. This cycle can repeat itself. My personal opinion is that patience will be rewarded. The second phase takes longer than the first, and NWBO appears to believe the second wave initiates somewhere between 8 (4th injection) and 32 weeks (6th injection). Immune memory, if it is to occur, is the last phase.

My position is that there are early glimpses of systemic response. IMHO. I also posted other messages than just giving a layman's description of cancer mutation and the need to inject multiple tumors. Multiple injections, IMHO, are also important to soften the large tumor battlefields and it gives DC's the opportunity to gather more tumor debris at an earlier stage..... I give Foxhound the floor on this matter (cancer mutation rate) (I think he is correct), but I have read a great deal in the past regarding how cancer escapes various therapies. Mutation is one way, immunosuppression is yet another. There are approximately 11 identified Hallmarks of Cancer. I stand by my comment that, IMHO, every time you inject a new tumor, you are essentially creating a new vaccine due to the rapid rate at which mutation occurs.

I highly suggest anyone interested in cancer biology, suppression and escape review the "Hallmarks of Cancer" and the "Hallmarks of Cancer, the Next Generation." It is a peer reviewed article that has been cited over 15,000 times in other peer reviewed articles. The latter discusses mutation rate and chromosome abnormalities. You also get a very good feel for why large tumors are exceptionally good at creating a tumor suppressing environment.

Long said:

I was going to respond also, but yours is more thorough. Just one additional comment:

From the limited data we have seen so far, the trend certainly seems toward an increasing systemic response with time and additional injections; from the webcast slide:
- 13 of 20 3-injection patients have seen 'early positive responses (tumor cell death, tumor shrinkage and/or stopping progression of disease)
- 9 of 9 4-injection patients have seen 'early positive responses'; the sarcoma patient is one of these
- Allan Butler, a 6-injection patient, has seen his incurable stage 4 pancreatic cancer and metastases in other parts of his body improve enough that he is back to a normal life with 18 mo OS and counting when SoC OS median is 9 mo.

So at the worst, I think what could be said is early indications are that there might be a systemic response. Certainly there is NOT data that there is a weak systemic response.