As one antibody after another gets stacked on the growing pile of failed attempts to tackle lupus, scientists are flagging CAR-T therapies — which have done wonders in the cancer space — as a potential one-off treatment for the autoimmune disease, with some impressive mice data now available.
Their preclinical trial, the University of Tennessee Health Science Center researchers wrote in a Science paper, “provided unambiguous confirmation that CAR T cell therapy profoundly affects autoimmune disease progression in both NZB/W and MRL-lpr mice.”
Like rituximab — a Roche drug approved for rheumatoid arthritis but failed to make a dent in lupus — the CAR-T therapy works by depleting B cells, which are believed to cause a rampage in the body with a swath of autoantibodies. But unlike rituximab, the CAR-T cells induce target cell death by a direct mechanism, without requiring help from macrophages.
By targeting CD19, a marker present on almost all B cells, CAR-T therapy has shown remarkable potency and lasting effect in a number of blood cancers like B cell lymphoma.
That’s the effect they want to replicate in the lupus mouse models, and to a large extend it’s what they observed: Most mice that received the CAR-T treatment lived significantly longer than the control group, living as much as one year after the injection, with the CAR-T cells still active in vivo for that duration. CD19 expression was also not detected in spleens, skin and kidney of treated mice.
“Cell-based therapies provide further advantages over antibodies because CAR T cells require only a single administration, migrate to multiple lymphoid tissues and organs in the recipient, and develop into both effector and memory cell populations,” the researchers, led by Marko Radic, wrote.
Meanwhile, the team also noted differences in the three murine viral vectors used to genetically engineer the T cells — with amphotropic murine leukemia virus (A-MLV) retrovirus leading the pack.
A quick check on clinicaltrials.gov suggests that Shanghai GeneChem initiated a 5-person trial to test a similar approach in China, though the results are not available.
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