IGM-2537 bound with high affinity and avidity to CD123. In vitro, IGM-2537 engaged both CD123 and CD3 to induce potent T-cell activation and T-cell mediated cytotoxicity of CD123+ AML cells, and autologous CD123+ basophils and plasmacytoid dendritic cells (pDCs). Though IGM-2537 demonstrated comparable maximal killing activity to a comparator IgG TCE, IGM-2537 demonstrated minimal cytokine release.
IGM-2537 bound to human CD123 with high affinity, avidity, and specificity. Furthermore, IGM-2537 bound a unique epitope of human CD123 in domain 2 which does not overlap with IL-3. IGM-2537 co-engaged with both CD123 and CD3 antigens, leading to T cell-redirected killing of AML cell lines with concomitant T cell activation.