Is this the future?

I

If we believe that memory B cells are a problem them we may need to get rid of them. The problem is we have been stuck with the antibody approach, were we use antibodies to target B cells. The problem is that these clear out the blood but may not touch the cells in the lymph glands or the bone marrow and really don’t get into the brain very well.

We know that CD8 T cells can get into the brain in MS as they are the dominant T cell type in the MS brain. What if we could programme the T cells to destroy the B cells. They can get every where and they release their own killing toxin when they find their target. They could clear out the brain and the bone marrow.

We can make CD8 T cells to get rid of memory B cells. One way is using CD19 CAR-T. Here you get the antibody binding to CD19 bit of an antibody and engineer the tail to cause T cell activation so when you create a vector to infect T cells so it expresses CD19 and the signalling molecule.

However that will kill too many different B cells and won’t kill the antibody making cells, but you can get them by making the CD8 cells target B cell maturation antigen

Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma.

Sommer C, Boldajipour B, Kuo TC, Bentley T, Sutton J, Chen A, Geng T, Dong H, Galetto R, Valton J, Pertel T, Juillerat A, Gariboldi A, Pascua E, Brown C, Chin SM, Sai T, Ni Y, Duchateau P, Smith J, Rajpal A, Van Blarcom T, Chaparro-Riggers J, Sasu BJ.Mol Ther. 2019 Apr 8. pii: S1525-0016(19)30165-0

However the problem is getting rid of the CAR T after they have done their job. Otherwise you have no B cells for life and infections will occur There are solutions but will they work? They will be tested in cancer first.

Read the story of the living drug for cancer on the BBC website today for more details.

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