Breakthrough in Autoimmune Therapy: Allogeneic CAR-T Cells Show Promise

In a groundbreaking development, three patients with autoimmune diseases have responded positively to allogeneic CAR-T therapy, a significant milestone for this "off-the-shelf" cell therapy technology. The study, conducted in China and published in the prestigious journal Cell, sheds light on the potential of this innovative approach in treating autoimmune conditions, which have traditionally been challenging to manage.

Unlocking the Potential of Allogeneic CAR-T Therapy for Autoimmune Diseases

Engineered CAR-T Cells Target B Cells

A team of researchers, led by clinical immunologist Huji Xu, Ph.D., of Tsinghua University in Beijing, engineered CAR-T cells from donors to target CD19, a protein found on the surface of B cells. The researchers also took steps to prevent conflicts between donor cells and host cells by knocking out human leukocyte antigen and amplifying the cells negative for CD3. This innovative approach aimed to harness the power of CAR-T technology, which has been successful in treating B cell malignancies, and apply it to the realm of autoimmune diseases, where B cells have gone rogue.

Promising Results in Autoimmune Conditions

The researchers intravenously infused the engineered CAR-T cells into one patient with immune-mediated necrotizing myopathy (IMNM) and two patients with diffuse cutaneous systemic sclerosis (dcSSc). The patients first underwent a standard preconditioning treatment of fludarabine and cyclophosphamide and then stopped taking immunosuppressants. The researchers closely monitored the patients' blood to track the CAR-T cells.Within one to two weeks, the engineered CAR-T cells proliferated within the patients, and B cells began to disappear until they were undetectable. In the IMNM patient, B cells rebounded by six months after treatment, while the two dcSSC patients saw their B cells bounce back by month three. However, the B cell reset had a profound impact on the patients' conditions.

Significant Clinical Improvements

The IMNM patient went into remission at month two, which lasted through to month six and was accompanied by an increase in muscle mass and improved quality of life. The dcSSC patients saw significant improvements in their American College of Rheumatology Composite Response Index in Systemic Sclerosis scores, reaching 0.99 in the first month and sustaining that score through month six. Scores greater than 0.6 are considered an improvement. They also experienced improved skin elasticity, lung function, cardiac function, and reduced fibrosis.Remarkably, none of the three patients showed any signs of rejecting the transplanted cells, a common concern with allogeneic therapies.

Implications for the Future of Autoimmune Treatments

The study, sponsored by Shanghai-based Bioray Laboratories, represents a significant breakthrough in the field of autoimmune disease treatment. According to analysts at William Blair, this is the first clinical proof-of-concept supporting the therapeutic potential of an allogeneic CAR-T therapy for the treatment of autoimmune diseases.The data from this study is expected to provide a boost to biotechnology companies currently developing allogeneic CAR-T cell autoimmune therapies, including CRISPR Therapeutics, Allogene, and Poseida, as well as firms working on other CAR-T therapies for autoimmune diseases, like Cabaletta.While the results remain to be scaled to broader patient populations, the study authors have highlighted the promise of a donor-derived, off-the-shelf allogeneic CD19-targeted CAR-T therapy for autoimmune diseases. This breakthrough could pave the way for more effective and accessible treatments for patients struggling with these debilitating conditions.