Antibody-conjugated mesenchymal stromal cell drug delivery system for the treatment of autoimmune diseases in mice

Autoimmune diseases (AIDs), such as psoriasis and rheumatoid arthritis, are driven by immune dysfunction, leading to chronic inflammation and tissue damage. Mesenchymal stromal cells (MSCs) possess immunomodulatory and tissue repair properties; however, the therapeutic applicability of MSCs faces limitations due to the low homing efficiency upon systemic infusion. Inspired by antibody-drug conjugates (ADC), here we develop an antibody-conjugated MSC-based drug delivery system (AcM-DDS) that combines CD4 monoclonal antibody-conjugated MSC (CD4-mBMSC) with liposome-encapsulated Cedirogant, a RORγt inverse agonist. AcM-DDS targets CD4⁺ T cells, key drivers of AID, and precisely delivers RORγt antagonists to suppress Th17-mediated inflammation. In mouse models of imiquimod-induced psoriasis and collagen-induced arthritis, AcM-DDS enhances MSC homing to inflamed tissues, reduces Th17 activity, lowers pro-inflammatory cytokine production, and preserves cartilage and bone integrity. Thus, our results indicate the promising applicability of our engineered platform for targeted immune modulation and provide support for the suitability of this therapeutic approach for the treatment of AIDs. Antibody-conjugated Mesenchymal stromal cells (Ac-MSC) carrying internalized therapeutic agents represent a promising therapeutic approach for the treatment of autoimmune disease. Here, an ac-MSC-based drug delivery system, consisting of anti-CD4 antibody-conjugated MSCs loaded with a RORγt inverse agonist, is engineered to achieve selective targeting of pathogenic CD4 T cells and to deliver therapeutic benefits in mouse models of psoriasis and arthritis.