IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect

Don M. Benson, Courtney E. Bakan, Shuhong Zhang, Shauna M. Collins, Jing Liang, Shivani Srivastava, Craig C. Hofmeister, Yvonne Efebera, Pascale Andre, Francois Romagne, Mathieu Bléry, Cécile Bonnafous, Jianying Zhang, David Clever, Michael A. Caligiuri, Sherif S. Farag

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

Multiple myeloma (MM) patients who receive killer cell Ig-like receptor (KIR) ligand-mismatched, T cell-depleted, allogeneic transplantation may have a reduced risk of relapse compared with patients who receive KIR ligand-matched grafts, suggesting the importance of this signaling axis in the natural killer (NK) cell-versus-MM effect. Expanding on this concept, IPH2101 (1-7F9), an anti-inhibitory KIR mAb, enhances NK-cell function against autologous MM cells by blocking the engagement of inhibitory KIR with cognate ligands, promoting immune complex formation and NK-cell cytotoxicity specifically against MM cell targets but not normal cells. IPH2101 prevents negative regulatory signals by inhibitory KIR, whereas lenalidomide augments NK-cell function and also appears to up-regulate ligands for activating NK-cell receptors on MM cells. Lenalidomide and a murine anti-inhibitory NK-cell receptor Ab mediate in vivo rejection of a lenalidomide-resistant tumor. These mechanistic, preclinical data support the use of a combination of IPH2101 and lenalidomide in a phase 2 trial for MM.

Original languageEnglish (US)
Pages (from-to)6387-6391
Number of pages5
JournalBlood
Volume118
Issue number24
DOIs
StatePublished - Dec 8 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Benson, D. M., Bakan, C. E., Zhang, S., Collins, S. M., Liang, J., Srivastava, S., Hofmeister, C. C., Efebera, Y., Andre, P., Romagne, F., Bléry, M., Bonnafous, C., Zhang, J., Clever, D., Caligiuri, M. A., & Farag, S. S. (2011). IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood, 118(24), 6387-6391. https://doi.org/10.1182/blood-2011-06-360255