CAR-T cell therapy and PML

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CAR-T is a type of therapy where you get T cells to recognse a target by introducing the antigen-binding bit of antibodies attached to a T cell activating bit. One approach s to make them CD19 specific so they can root out and kill any CD19 expressing B cell. It could scrub the brain clean of CD19 B cells and I have heard one opinion leader from US saying they planned to use CAR-T cells in MS. It is on thing to do this in someone who is going to die due to the B cell cancer, but MS is a different issue. I think it is bonkers, because whilst you may deplete all B cells, the problem is that in these early studies there is no way to turn these T cells off and they could deplete your B cells forever and this means infection in the long run. In this paper another problem that has surfaced and this is PML. This should make alarm bells ring for this approach. However, if you can turn these cells off or get rid of them and make them more specific I think there could still be mileage in the approach

Progressive multifocal leukoencephalopathy after CAR T therapy. Sdrimas K, Diaz-Paez M, Camargo JF, Lekakis LJ. Int J Hematol. 2020 Mar 3. doi: 10.1007/s12185-020-02840-x. [Epub ahead of print]

Progressive multifocal leukoencephalopathy (PML) remains a life-threatening central nervous system infection in immunocompromised patients. PML has not been described as a cause of encephalopathy after CAR T therapy. We report the first case of PML 7 months after lymphodepleting chemotherapy with fludarabine/cyclophosphamide and anti-CD19-directed CAR T therapy in a patient with lymphoma who relapsed fast after a previous autologous hematopoietic stem cell transplant.

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