Antigen CD111 as a new specific diagnostic and therapeutic marker for polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs)
This invention concerns a method for detecting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in a biological sample by employing the CD111 antigen as a marker for said cells, and the use of said marker as an immunotherapeutic target.
It has been observed that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have an immunosuppressive role in different diseases, as well as the ability to inhibit the antitumor response of immune cells. In the context of transplantation, the direct identification and selection/elimination of PMN-MDSC cells would enable a functional recovery of the anti-leukaemic activity of NK cells, while, in patients with neoplasia, it would make it possible to easily identify their presence in peripheral blood, and to evaluate both the effectiveness of the therapy and any relapse of the disease. However, to date no unique marker for the identification of PMN-MDSCs has been identified. Furthermore, direct identification of PMN-MDSCs in peripheral blood according to currently known methods is impossible. Current procedures are complex and involve the use of density gradients, phenotypic characterization and functional tests. According to this invention, the CD111 marker makes it possible to distinguish PMN-MDSCs from their neutrophilic counterpart in a direct way. This invention also concerns a PMN-MDSC cell inhibitor for the treatment of cancers or infectious diseases, as it targets the CD111 marker.
- Solid tumors, paediatric or adult haematological tumors for the restoration of the anti-tumor functions of the effector cells of the immune system
- Diagnostic kits for the determination of CD111 in biological samples of different origin and kit for the depletion of PMN-MDSC cells from a biological product used for immunotherapy (stem cell transplantation) before infusion into the patient
- Stem cell transplantation and Development of anti-CD111 mAb to be used in vivo for immunotherapy
- Direct identification of PMN-MDSCs from liquid sample (ascites, synovial fluids) or solid tissue (fresh tissue biopsies, including paraffin embedded or cryopreserved ones) with no need for complex separation and characterization procedures
- The selective elimination of PMN-MDSCs enables the restoration of the antitumour functions of the effector cells of the immune system