The CD28/CTLA-4 pathway controls both T-cell activation and regulatory T-cell down regulation. CD28 receptor is expressed on the surface of the majority of naïve T-cells and is the major co-stimulatory molecule to generate T-cell activation.

In contrast, CTLA-4, a CD28 homologue, is expressed on activated T-cells, especially regulatory T-cells (T-Reg), and has been historically described as the essential component of the regulation of immune self-reactivation. Therefore, the CD28/CTLA-4 pathway is believed to be at the heart of different autoimmune diseases such as rheumatoid arthritis.

FR104, a monoclonal antibody fragment and CD28 antagonist, selectively blunts CD28 co-stimulation while sparing the CTLA-4 co-inhibitory signal. The net effect of CD28 antagonism is down regulating effector T-cells while promoting T-Reg activity.