Autoimmune-Stricken Patients Respond to Allogeneic CAR-T Treatment

Three patients with autoimmune disorders have responded favorably to allogeneic CAR-T therapy, marking a breakthrough for the “off-the-shelf” cell therapy technology. According to experts at William Blair, the study, carried out in China, is the first indication of the possible use of allogeneic CAR-T therapy in treating autoimmune illnesses.

CAR-T cells were generated from donors and focused on CD19, a protein located on the exterior of B cells. The experiment was conducted by a large group of researchers at Tsinghua University in Beijing, led by immunologist Huji Xu, Ph.D. To eliminate issues between the donor and host cells, the team wiped off the human leukocyte antigen in the cells and subsequently increased the cells that were negative for CD3.

The targeting of CD19 is a relatively new therapy used to treat B cell tumors; however, it has not yet been successfully applied to treating B cells that have become dysfunctional, as is the case in autoimmune illnesses.

The therapeutic cells were administered intravenously to three patients: one with immune-mediated necrotizing myopathy (IMNM) and two with diffuse cutaneous systemic sclerosis (dcSSc). The patients first ceased using immunosuppressants and completed a typical preconditioning treatment with fludarabine and cyclophosphamide. After that, the researchers tracked the CAR-T cells by carefully monitoring the patients’ blood.

Within one to two weeks, the modified CAR-T cells multiplied within the patients, and B cells started decreasing until they were undetectable. B cells rebounded in the IMNM patient six months after the therapy, whereas the two dcSSc individuals had their B cells return by the third month.

The B cell reboot succeeded. The IMNM subject entered remission at month two, which persisted through month six and was followed by a rise in muscle mass and an improved quality of life. The dcSSc patients increased their ACR-CRISS ratings to 0.99 in the first month and maintained that level through the sixth month. Scores that exceed 0.6 indicate improvement. They also noticed increased skin elasticity, pulmonary function, heart function, and reduced fibrosis.

None of the three patients demonstrated any evidence that their organs were rejecting the donated cells.

According to William Blair analysts, the study represents “the first clinical proof-of-concept supporting the therapeutic potential of allogeneic CAR-T therapy for the treatment of autoimmune diseases, to our knowledge.” The analysts added that it’s not yet clear how much the treatment’s efficacy was influenced by changes to the cells’ genomes.

The results should be favorable to biotechs now researching allogeneic CAR-T cell treatments for autoimmune disorders, as well as companies developing alternative CAR-T therapeutics for autoimmune illnesses, such as Cabaletta.

While these results are yet to be expanded to larger patient groups, the study authors concluded that they hint at the prospect of a donor-focused allogeneic CD19-targeted CAR-T treatment for autoimmune disorders.

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