Autoimmune Patients See Breakthrough Response to Allogeneic CD19-Targeted CAR-T Therapy

Three patients with autoimmune diseases have shown positive responses to allogeneic CAR-T therapy, marking a significant first for the “off-the-shelf” cell therapy technology. Furthermore, this research, conducted in China and published in Cell on July 15, provides the novel evidence directed at the potential of this allogeneic CAR-T therapies in specifically treating autoimmune diseases.

First Steps: Exploring CD19-Targeted CAR-T Therapy for Autoimmune Conditions

Led by clinical immunologist, Dr. Huji Xu from Tsinghua University in Beijing, a large team of researchers engineered CAR-T cells from donors to target CD19, a protein present on B cells’ surface. They strategically removed the human leukocyte antigen (HLA) and amplified CD3-negative cells to mitigate potential immune conflicts between donor and host cells. Despite CD19 being a promising therapy for B cell malignancies, its application to address abnormal B cells, such as in the case of autoimmune diseases, has not been successful to date. As such, this study marks the first step in exploring the efficacy of CD19-targeted CAR-T therapy in treating autoimmune conditions.

Specifically, Xu and colleagues conducted a clinical study using engineered CAR-T cells that target CD19 to treat patients suffering from autoimmune diseases. They administered intravenous infusions of these therapeutic CAR-T cells to three patients: one with immune-mediated necrotizing myopathy (IMNM) and two with diffuse cutaneous systemic sclerosis (dcSSc). Prior to the treatment, all patients discontinued immunosuppressants and underwent preconditioning with fludarabine and cyclophosphamide. Following this regime, the researchers observed the CAR-T cells in the blood of the patients. 

Following infusion, significant effects on B cells were observed within one to two weeks. The CAR-T cells engineered to target CD19 began proliferating in the patients, leading to a marked reduction and eventual undetectability of B cells, crucial players in autoimmune responses. 

Long-term Responses Between 3–6 Months & Good Safety Profile Demonstrate Clinical Benefits

Long-term responses to the CAR-T cell therapy in the study revealed varying timelines for the return of B cells in patients. In the IMNM patient, B cells began to reappear six months after treatment initiation, while in the dcSSc patients, this rebound occurred by month three. Despite the resurgence of B cells, the treatment demonstrated substantial clinical benefits.

The IMNM patient experienced remission as early as month two lasting through to month 6, accompanied by notable increases in muscle mass and improvements in overall quality of life. Similarly, the dcSSc patients exhibited continuous improvement in their American College of Rheumatology Composite Response Index in Systemic Sclerosis scores from the first month throughout the six-month observation period. The patient scores were reported at 0.99, whereby scores greater than 0.6 are representative of improvement. These positive outcomes were reflected in enhanced skin elasticity, improved lung and cardiac functions, and reduced fibrosis.

Regarding safety and tolerance, none of the three patients displayed signs of rejecting the transplanted CAR-T cells, showcasing the therapy’s well-tolerated nature. 

Donor-Derived, Allogeneic CD19-Targeted CAR-T Therapy for Autoimmune Diseases

Bioray Laboratories sponsored the study, yielding findings that represent a significant milestone in advancing allogeneic CAR-T therapy for treating autoimmune diseases. According to analysts at William Blair, this study constitutes the first clinical proof-of-concept supporting the potential effectiveness of allogeneic CAR-T therapy in this field. However, uncertainties persist regarding the extent to which genetic modifications of the cells influenced treatment outcomes.

The same analysts suggest that these findings could energize biotechnology companies currently developing their own allogeneic CAR-T cell therapies for autoimmune conditions. This includes companies such as CRISPR Therapeutics, Allogene, Poseida, and others actively engaged in CAR-T therapies for autoimmune diseases like Cabaletta. Currently, drugmakers, including Novartis and Bristol Myers Squibb, are testing nearly 30 different CAR-T treatments for autoimmune diseases in clinical trials. These treatments cover conditions such as myositis, a muscle inflammation condition, and multiple sclerosis.

The study’s results validate the therapeutic potential of allogeneic CAR-T therapies in autoimmune diseases, potentially shaping future developments and investments in this field. Further, the potential of scaling these results to larger patient populations, highlights the promise of using donor-derived, off-the-shelf allogeneic CD19-targeted CAR-T therapy for treating patients with these conditions.

Related posts:

Kite to Invest in Next Generation Immunotherapy with Appia Bio Collaboration Decoding Overweight and Obesity: The Significance of Brain Structure Nikon Strengthens Global Presence in Drug Discovery with New BioImaging Labs Degrader-Antibody Conjugates (DACs): Targeted Protein Degradation for Therapeutics

Author

Bernice Lottering