Killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) (KIR3DL2)

Killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) is an inhibitory receptor primarily expressed on natural killer (NK) cells and a small subset of T cells [7, 12]. It belongs to the KIR family and is characterized by three extracellular immunoglobulin-like domains and a long cytoplasmic tail containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) [10, 12]. KIR3DL2 specifically recognizes HLA-A3 and HLA-A11 allotypes in a peptide-dependent manner, as well as the free heavy chain form of HLA-B27 [4, 10, 14]. In physiological conditions, these interactions provide inhibitory signals that regulate NK cell activation and maintain self-tolerance [11, 13]. In the context of disease, KIR3DL2 is highly and aberrantly expressed on the surface of malignant T cells in cutaneous T-cell lymphomas (CTCL), such as Sézary syndrome and mycosis fungoides, as well as in peripheral T-cell lymphoma (PTCL) and adult T-cell leukemia/lymphoma (ATL) [1, 5, 20, 21]. This restricted expression pattern makes it an ideal therapeutic target and diagnostic biomarker [9, 20]. The primary therapeutic agent targeting this receptor is lacutamab (IPH4102), a humanized monoclonal antibody designed to deplete KIR3DL2-positive tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP) [1, 2, 19]. Additionally, the interaction between KIR3DL2 and its ligands has been implicated in the pathogenesis of autoimmune diseases like ankylosing spondylitis and pemphigus foliaceus [3, 12, 14].

Other names

CD158kNKAT4p140Killer cell immunoglobulin-like receptor 3DL2MHC class I NK cell receptorKIR3DL2-HLA-A3/A11 complex

Lacutamab is a humanized monoclonal antibody that targets KIR3DL2-expressing cells to induce their depletion via antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) [1, 2]. CpG oligonucleotides bind to KIR3DL2 and promote receptor internalization and apoptosis in malignant cells [7, 11].