A Cart to destroy B cells in the brain.

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Antibodies againts the CD19 marker on B cells can clear out B cells from the blood and to some extent the lymph glands, but antibody doesn’t get into the brain very well and so will not clear out the brain very well. Even if it did get in the brain, as the antibodies often need natural killer cells/neutrohils to mediate the destuction and these cells are not attracted into the brain.

T cells can get into any tissue in any part of the body and if acrivated have no problem in getting into the brain. T cells have targets due to their antigen receptors, but you can engineer them to have new targets by inserting an antibody into them.

This antibody is engineered to exhibit T cell activation machinery and is called a CAR = chimeric antigen receptor. You put it into a CD8 kiler cell and the result is CAR-T-cell. This is specifically developed for each individual patient and involves reprogramming the patient’s own immune system cells which are then used to destroy their target.

So if you want to get the T cells to kill B cells you can give them a CD19 chimeric antigen receptor (an antibdoy on the cell surface and a T celll receptor signalling element). If you wan to kill plasma cells (antibody secreting cells you can make a BCMA (B-cell maturation antigen known as tumor necrosis factor receptor superfamily member 17) as it expressed by plasma cells. If you wanted to targetmemory B cells you could go APRIL receptor (Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B).

CART-19 is being used against B cell and plasma cell cancers and CAR-T therapy can cure people of their cancers. They can clear out the brain the bone marrow etc. But once you have made these T cells they will not only root out the B cell cancers where ever they are lurking but they will destroy ever B cell in the body……forever. Therefore, it is a potentially risky treatment and so used in people with life threatening problems. However, it has real potential if you could get rid of the CAR T cells once they have done the business to get rid of the pathogenic B cells or if you want T cells or ThGM, Th1 or Th17 etc. It would mean perhaps that you would have to re vaccinate your childhood infections if you remove plasma cells but remember you are not destroying the stem cells,early B cells so a new repertoire can regenerate.

In animals it has been shown that you can get rid of the anti B cell CAR-T -B cells using antibodies. They get them to express a molecule (which is designed not to bind to its natural target or signal), which can be targeted a commercially available antibody. Will this become a reality for humans?`Is this going to be good enough becuase will those CART cells be lurching in the places antibodies can’t reach

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