Replies to post #202204 on NorthWest Biotherapeutics Inc (NWBO)

[marzan]

this post needs to be stickied. Thanks flipper!

[Basin Street Blues]

Probably all true but they had 60% + tute shareholders , that gets them
a huge premium.

So net ,net ..

[sukus]

Stickied please moderator. Thank you.

[survivor1x]

Solid tumours from my understanding are not as homogeneous as blood cancers. That is why a CarT can have great responses in blood cancers. You kind of hit on that with selecting the Antigens, but the response rates they see in blood will not carry over to solid tumors IMO. The Toxicities are also a concern as you state. "IF" the DCVAX hypothesis is true and the cells are able to uptake patient/tumor specific targets(Direct builds on this with Tumor heterogeneity) present these to TILs and increase survival with little collateral damage, I can't see why this isn't a big fat DUH, why didn't BP think of that. Why wouldn't you treat the patient with the best possible targets? Why wouldn't you treat them with a drug with less toxicities? If it works, and I believe it does, it is off to the races. The problem is we have been conditioned to believe two separate "truths" with cancer care. 1. We have to show 1 size fits all treatment value in a very personal and not 1 size fits all disease. And 2.We have been thought that the cancer drugs must be toxic, otherwise how are they working.(A.F.s grapefruit comment)

[jondoeuk]

''Juno and Kite have near-term technologies only connected to 10% of the cancer market.''

$GILD/Kite has a number of TCRs trials for a range of solid tumours and some others are preclinical.

''They work on leukemia and lymphoma. They do this by going after antigen(s) that make up both healthy and cancerous cells. They kill all healthy B-cells in the body.''

Some pts can recover. In other cases 'on switches' may overcome this http://www.pnas.org/content/115/46/E10898.long $GILD will be using small molecules.

''I can't impress on people enough how this is not the way it works with solid cancer. One poster here thinks Car-Ts can work on solid tumors, but they have not come close to approval.''

For some I think it is possible by engineering, bi/tri-specific, cytokine secreting controlled versions https://www.jci.org/articles/view/83416 https://academic.oup.com/neuro-oncology/article-abstract/20/4/506/4159414 https://link.springer.com/article/10.1007%2Fs00262-012-1202-z

''They can't attack solid tumors the same way they attack lymphoma and leukemia or they would always kill the patient.''

With a fully human CAR you reduce SAEs https://pbs.twimg.com/media/Dtg18DvWkAYhstu.jpg and as I said above these can be controlled. $GILD has one in a trial https://ash.confex.com/ash/2018/webprogram/Paper113731.html and working on a number of others.

''Instead, just like peptide vaccines or restricted DCVaccines, they are trying to find the right antigens and neoantigens to attack and only kill cancer cells. Just like Celldex and Immunocellular, they have not found the right cocktail of antigen(s) and neoantigen(s).''

$GILD is working on both autologous and allogeneic neoantigen reactive TCRs https://www.nature.com/articles/nm.3359 https://www.nature.com/articles/nm.4051

''DCVax, on the other hand, has a product that can target 90% to 100% of the cancer market without artificially selecting things like killing all healthy B-cells in the body to win. Essentially, 1st and second generation Car-T's are being asked to do things the body would never do because of nature's evolutionary safety defaults. DCVax instead works within the evolutionary safety defaults.''

Many others are working on neoantigen vaccines. For me $GRTS have shown that their in silico selection and delivery methods are likely going to be much better than others in the space http://cancerres.aacrjournals.org/content/78/13_Supplement/5722 http://cancerres.aacrjournals.org/content/78/13_Supplement/724