Three people with autoimmune diseases have responded positively to allogeneic CAR-T therapy, marking a first for the “off-the-shelf” cell therapy tech.
The study, conducted in China and published in Cell on July 15, is the first sign of the potential of allogeneic CAR-T therapies in treating autoimmune diseases, according to William Blair analysts.
A large 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. They also knocked out human leukocyte antigen in the cells and then amplified the cells negative for CD3, in order to prevent conflicts between donor cells and host cells. CD19 targeting is an emerging therapy for treating B cell malignancies, but it hasn’t successfully been used to treat B cells that have gone rogue, as is the case in autoimmune diseases.
Xu and colleagues intravenously infused the therapeutic cells into one patient with immune-mediated necrotizing myopathy (IMNM) and two patients with diffuse cutaneous systemic sclerosis (dcSSc). The patient trio first stopped taking immunosuppressants and underwent a standard preconditioning treatment of fludarabine and cyclophosphamide. The researchers then monitored the patients’ blood to track the CAR-T cells.
In 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.
The B cell reset worked. 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 improved their American College of Rheumatology Composite Response Index in Systemic Sclerosis scores to 0.99 in the first month and sustained that score through month six. Scores greater than 0.6 are considered an improvement. They also saw improved skin elasticity, lung function, cardiac function, and fibrosis.
None of the three patients showed any signs that their bodies were rejecting the transplanted cells.
The study, sponsored by Shanghai-based Bioray Laboratories, represents “the first clinical proof-of-concept supporting the therapeutic potential of an allogeneic CAR-T therapy for the treatment of autoimmune diseases, to our knowledge,” according to a note from William Blair analysts. The analysts also pointed out that it’s unclear how much tinkering with the cell’s genomes influenced treatment efficacy.
The data should be a boon to biotechs currently developing allogeneic CAR-T cell autoimmune therapies of their own, according to the analysts, including CRISPR Therapeutics, Allogene, and Poseida, as well as for firms developing other CAR-T therapies for autoimmune diseases, like Cabaletta.
“We view the additional data in IMNM (i.e., myositis) and SSc as supportive of the continued evaluation of CAR-Ts in additional indications outside lupus,” the analysts wrote in the report.
While these results remain to be scaled to broader patient populations, the study authors wrote that they point to the promise of a donor-derived, off-the-shelf allogeneic CD19-targeted CAR-T therapy for autoimmune diseases.