Non‐Redundant Roles of T Cell Costimulation Pathways in Inflammatory Arthritis Revealed by Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN‐101)

The study explores acazicolcept (ALPN‐101), an Fc fusion protein designed to inhibit CD28 and ICOS costimulation, for treating inflammatory arthritis. Acazicolcept effectively blocked CD28 and ICOS interactions, surpassing single-pathway inhibitors. In a collagen-induced arthritis model, acazicolcept outperformed abatacept in reducing disease. It also curbed proinflammatory cytokine production and exhibited unique gene expression effects. Findings suggest that dual inhibition of CD28 and ICOS pathways by acazicolcept could offer a more potent approach for managing rheumatoid arthritis and psoriatic arthritis than targeting either pathway alone.