An Fc fusion protein comprised of a human inducible T-cell costimulator ligand (ICOSL) variant immunoglobulin domain (vIgD) that binds to both inducible T-cell costimulator (ICOS; CD278) and cluster of differentiation 28 (CD28), with potential immunomodulating activity. Upon administration, CD28/ICOS antagonist ALPN-101 targets and binds to both CD28 and ICOS expressed on certain T-cells. This prevents the activation of CD28 and ICOS by its ligands, thereby blocking the two T-cell costimulatory pathways and the resulting T-cell activation. CD28 is involved in initiation of the pathogenic process in graft versus host disease (GVHD). Following initial activation, CD28 is often downregulated while ICOS is upregulated, possibly sustaining GVHD. Dual blockade of CD28 and ICOS may be superior to individual blockade of CD28 or ICOS alone.