[readittwice]

Since there are people here that seem to know a bit about this stuff, I will take the chance to ask some naive questions ;)

Do I have this right that CAR T-cells have this engineered B-cell/antibody like receptor that recognizes antigens only on the cell membrane. While the regular T-cell receptor can look into cells as well? And that's why the T-cell receptor is potentially better at recognizing solid cancers?

So cancers usually create this immunosuppresive environment, wouldn't this stop this engineered T-cells as well?

[dm319]

Yes, CAR-Ts are really a B cell receptor (otherwise known as an antibody) grafted onto a T cell. Antibody directly binds things like proteins, and usually targeted to things found on cell membranes.

Also on the cell membrane is MHC-1, which shows a short (9-11 amino acid) fragment of protein produced from inside the cell. Our T cells are trained in our T cell kindergarten (the thymus) to not identify our usual self proteins, but detects anything different. They have already been demonstrated to identify single amino acid changes from normal.

Yes, the micro-environment means the immune cells reach a dynamic equibrium. This is because when a cancer presents to healthcare, it is already a chronic process. The T cells are termed 'exhausted', but it's debatable whether this is a good term for it, because they are still active.

A lot of cancer treatment 'shakes up' the microenvironment. This can be enough to tip into a cure. When you make CAR-Ts and adoptive TILS you either pick healthy T cells not involved in the cancer or buff them up in the lab, both in numbers and health.

The hope is that a refreshed army of T cells will push that dynamic equilibrium towards a cure.

[acchow]

9-11 amino acids sounds very short - only 18-22 bits of information. How do we decide something has gone wrong from only an 18 bit slice?