WT1-targeted IL-2-based fusion protein CUE-102

A Fc-engineered fusion protein composed of two human leukocyte antigen (HLA) molecules presenting a Wilms’ tumor 1 (WT1) peptide that are each linked to two affinity-attenuated interleukin 2 (IL-2; IL2) molecules, with potential immunomodulating and antineoplastic activities. The HLA molecules presenting a WT1 peptide are peptide-HLA-A*0201 major histocompatibility complex (pMHC) derived from the WT1 peptide encoded by the amino acids 37-45. Upon administration of CUE-102, the pMHC moiety selectively targets, binds to and activates the T-cell receptor (TCR) on WT1-specific T lymphocytes. By selectively delivering the IL-2 moiety to the CD8-positive T cells, the IL-2 moiety specifically binds to IL-2 receptors on tumor-specific effector T cells and mediates the selective expansion of WT1-specific T-cells. This increases the T-cell-mediated anti-tumor immune response against WT1-expressing tumor cells and thereby eliminates tumor cells. The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. WT1, a co-fetal protein and tumor-associated antigen (TAA), is overexpressed in a number of cancers. The IL-2 variant (‘not-alpha’ IL-2) preferentially activates tumor-specific CD8+ T cells and does not prefer to bind to the IL-2 receptor alpha subunit; this minimizes systemic effects on non-tumor-specific T cells. This minimizes induction of pro-inflammatory cytokines release and non-specific and systemic activation of immune cells.