KIR3DL2 as a biomarker and therapeutic target for diagnosis, prognosis and treatment of cutaneous and non-cutaneous peripheral T-cell lymphoma
Peripheral T-cell lymphomas (PTCLs) are heterogeneous and uncommon non-Hodgkin’s tumor diseases characterized by an aggressive clinical course and a mostly poor outcome with current treatment strategies. One of the most urgent difficulties is to properly classify these diseases to provide the patient with the most adapted treatment, such as cell-targeted chemotherapy, radiotherapy and/or marrow bone transplantation. Among the cutaneous PTCL, Sézary syndrome and transformed mycosis fungoides are the most prevalent cutaneous T-cell lymphomas.
There is a need for targeted therapy. Previous studies demonstrated that treatment of Sézary cells with the Janus kinase (JAK) inhibitor efficiently promotes phospho-STAT3 dephosphorylation and induces Sézary cell apoptosis. Regarding some physiological aspects of Sezary’s syndrome, it has notably been shown that a combination of 4 biomarkers are of special interest, since PSL3, TWIST, KIR3DL2 and NKp46 were shown to be overexpressed in T-cells from Sézary and transformed mycosis fungoides individuals. However, there are confusing data whenever KIR3DL2 should be considered as a relevant biomarker.
Killer immunoglobulin-like receptors (KIR) represent a family of receptors that are used by human Natural Killer (NK) cells and T-lymphocyte subsets to specifically recognize MHC class I molecules. KIR3DL2 belongs to the KIR receptor family. KIR3DL2 has been reported to be a candidate for target therapy, since a monoclonal antibody that binds to KIR3DL2 is able to induce an antibody-dependent cellular cytotoxicity (ADCC) against malignant T-cells expressing KIR3DL2.
The present invention relates to a ligand molecule that specifically binds to KIR3DL2 at the surface of KIR3DL2 expressing malignant T-cells for the treatment of lymphomas. It also relates to the in vitro use of a level of expression of KIR3DL2 is a biomarker useful for diagnosing and/or monitoring a lymphoma.