Replies to post #380548 on NorthWest Biotherapeutics Inc (NWBO)

[MI Dendream]

King, “All patients are living longer.”

I agree totally with Biosect. I think of cancer cells like normal flora. This analogy helps me. If you give an antibiotic that kills one of your flora, another expands or a new transplants to take its place. I think that some day we will be able to smack cancer with the right cell at the right time. I believe in Linda Liau.

GBM is the mother of all cancers for multiple reasons, one being that it morphs faster than almost any other. Another being that the brain is immunoprivelaged, meaning it is harder for cells to access the tumor but not impossible, and still another being that the skull is fixed volume with a drain at the base. This presents difficulties with added pressure as the brain stem controls breathing and heart rate. Expansion of a tumor too large can kill which means you need the immune system to be in control of volume as well.

Some tumors will grow and/or mutate too fast for the single punch, but Linda will get us there. Or at least lay the path for others to expand upon. Dendritic cells check!

[jondoeuk]

Car-T cells (a type of immune therapy that boomed and has had a lot of focus), for instance, are really good at killing very particular cells with particular markers. That includes beneficial cells often.

There are potential ways to overcome that https://stm.sciencemag.org/content/13/591/eabd8836.short https://www.mdpi.com/2072-6694/12/9/2612/htm

Unfortunately, those cells are highly engineered and don't stay in the body

For some types, peak expansion is more important than long-term persistence https://ascopubs.org/doi/full/10.1200/JCO.20.01467 https://ashpublications.org/bloodadvances/article/4/19/4898/464200/Tumor-burden-inflammation-and-product-attributes

and frequently they do not therefore educate the body after they are done, as to what to look for to prevent a recurrence of that cancer

Data from GILD (translational data shows there isn't long-term persistence in many, if not most) https://www.nasdaq.com/press-release/new-four-year-data-show-long-term-survival-in-patients-with-large-b-cell-lymphoma

So recurrence is a dirty secret of Car-T cell treatments.

No, it isn't. GILD's data show that despite optimal product attributes, a 'favourable' TME and robust CAR-T cell expansion, there is incomplete tumour elimination and around 15% of patients relapse with target-negative cancer cells. They are working on ways to overcome that, with an anti-CD19/CD20 CAR-T https://cancerimmunolres.aacrjournals.org/content/4/6/498.long

But you need multiple mechanisms.

NTLA is using their own screening platform (CRISPR/Cas9) to identify enhancing edits for CAR-T and TCR-T cell therapies. These look to improve trafficking, infiltration, potency and persistence, while also preventing exhaustion in the TMEs. They have identified both known and potential novel regulators. Importantly, some knockout targets accumulate in multiple, distinct TMEs, while others are TME specific.