ANTI-KIR STRATEGY IN CANCER TREATMENT

作者：Benson D M Jr^*

来源：Drugs of the Future, 2013, 38(2): 99-105.

DOI：10.1358/dof.2013.38.2.1928594

• Natural killer cells
• KIRs
• Monoclonal antibodies
• IPH-2101
• Anticancer therapy

Natural killer (NK) cells, a lymphocyte subset of the innate immune system, were originally named in reference to their ability to lyse tumor cell targets independent of secondary signals. How NK cells recognize and kill target cells was a matter of intense investigation, and it is now understood that NK cells express a rich diversity of activating and inhibitory receptors through which cytotoxicity is modulated. Inhibitory killer immunoglobulin-like receptors (KIRs) represent an important family of NK cell receptors which engage cognate ligands expressed on candidate target cells to prevent a cytotoxic response. Target cells that have lost expression of KIR ligands or display mutated or mismatched KIR ligands are susceptible to NK cell-mediated lysis, a phenomenon that has been exploited in the setting of haploidentical allogeneic stem cell transplantation. Extrapolating on this concept, monoclonal antibodies (MAbs) against inhibitory KIRs are now in development to block the KIR ligand interaction and prevent the inhibitory signaling that dampens or prevents NK cell cytotoxicity. IPH-2101 represents a first-in-class MAb against common inhibitory KIR in development as a novel anticancer therapy. The present work serves to review and summarize the basic biology of the KIR ligand interaction and the clinical translation of these principles in the treatment of malignancy.

• 出版日期2013-2