Background/Purpose: Immunotherapies targeting antigens expressed on B cells are currently being explored as treatments for autoimmune disorders like antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), systemic sclerosis (SSc), and systemic lupus erythematosus/lupus nephritis (SLE/LN).  CD20-targeting antibodies have been used to treat autoimmune diseases for the past two decades, while CD19-targeting CAR T cells have recently demonstrated encouraging efficacy and tolerability in treating patients with SLE, IIM, and SSc.¹   However, each of these therapies when used alone may spare pathogenic immune cells.  Targeting CD20 alone allows plasma cells that lack CD20 expression to escape.  Targeting CD19 alone may lead to the escape of pathogenic CD20 positive T cells that have been associated with certain autoimmune diseases.  Combining the established benefit of CD20 targeting with CD19 CAR T cell therapy has the potential to more effectively eliminate pathogenic cells and provide durable responses in patients with autoimmune disease.

Methods: IMPT-514, a CD19/CD20 bispecific CAR T cell product candidate, was manufactured using CD62L-enriched cells from donors with AAV, IIM, SSc, and SLE/LN.  These CAR T cells were phenotypically characterized by flow cytometry and tested for their ability to eliminate autologous IgG-producing B cells and cytokine production.  

Results: IMPT-514 CAR T cells generated from these donors are enriched in naïve and central-memory phenotypes and show clinically meaningful CAR expression and activity including the ability to eliminate autologous IgG-producing B cells and produce interferon-gamma (IFN-γ). Importantly, patient-derived IMPT-514 cells showed the same level of effector function as IMTP-514 CAR T cells manufactured from healthy donors.  

Conclusion: IMPT-514 has the potential to be an effective agent for the treatment of a variety of B-cell–driven autoimmune diseases such AAV, IIM, SSc, and SLE.  These results have supported a clinical trial being opened for its use in SLE/LN (NCT06153095).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/manufacturing-of-impt-514-a-cd19-cd20-bispecific-car-t-cell-product-candidate-as-a-potential-treatment-of-patients-with-autoimmune-diseases/