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Saturday, October 05, 2024

Treatment of Autoimmune Diseases

I have a thought so blindingly obvious that I don’t know why I haven’t read about it. First the thought then wondering why I haven’t found it written.

The idea is to treat with a chimera of an antibody to a tissue specific antigen and PDL1 (note how quickly it can be stated).

PDL1 (programmed death ligand 1) interacts with PD1 (programed death 1) On Kiler T cells and Natural Killer cells. The acronyms suggest that these cells then die. However, it is now known that they live on without killing the cell which displays PDL1. Blocking this “checkpoint” Is a very major dramatic Nobel Prize winning step towards effective immunotherapy of cancer.

Killing by lymphocytes is often a problem: Type 1 diabetes, Multiple sclerosis, Celiac Disease, Ulcerative Colitis and other less common disorders. It seems obvious that the PDL1/PD1interaction could be very useful. A problem with immunosuppressants is that they leave the patient vulnerable to infections. They are still used, however it clearly would be useful to focus the immunosuppression on the tissue where the immune response is causing trouble.

This should be easy if there is a monoclonal antibody which binds to that tissue. For example pancreatic Islet cells (beta cells) display a characteristic antigen Zinc Transporter-8 (ZnT8) cells There is a monoclonal antibody to this antigen . It seems to me that a chimera of that antibody and PDl1 is worth exploring.

It is possible that by the time Diabetes is diagnosed it is too late (there are beta cells in the pancreases of people with type 1 diabetes but they may have survived by becoming irreversibly dormant). Also Islet cells for transplant might usefully be decorated with the chimera.

For multiple sclerosis and related diseases a myelin specific might be useful. Such antibodies exist and create trouble when not attached with PDL1.

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