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IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect.
Blood 2011; 118(24):6387-91Blood

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.

Authors+Show Affiliations

Division of Hematology, The Ohio State University, Columbus, OH, USA. don.benson@osumc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22031859

Citation

Benson, Don M., et al. "IPH2101, a Novel Anti-inhibitory KIR Antibody, and Lenalidomide Combine to Enhance the Natural Killer Cell Versus Multiple Myeloma Effect." Blood, vol. 118, no. 24, 2011, pp. 6387-91.
Benson DM, Bakan CE, Zhang S, et al. IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood. 2011;118(24):6387-91.
Benson, D. M., Bakan, C. E., Zhang, S., Collins, S. M., Liang, J., Srivastava, S., ... 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), pp. 6387-91. doi:10.1182/blood-2011-06-360255.
Benson DM, et al. IPH2101, a Novel Anti-inhibitory KIR Antibody, and Lenalidomide Combine to Enhance the Natural Killer Cell Versus Multiple Myeloma Effect. Blood. 2011 Dec 8;118(24):6387-91. PubMed PMID: 22031859.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. AU - Benson,Don M,Jr AU - Bakan,Courtney E, AU - Zhang,Shuhong, AU - Collins,Shauna M, AU - Liang,Jing, AU - Srivastava,Shivani, AU - Hofmeister,Craig C, AU - Efebera,Yvonne, AU - Andre,Pascale, AU - Romagne,Francois, AU - Bléry,Mathieu, AU - Bonnafous,Cécile, AU - Zhang,Jianying, AU - Clever,David, AU - Caligiuri,Michael A, AU - Farag,Sherif S, Y1 - 2011/10/26/ PY - 2011/10/28/entrez PY - 2011/10/28/pubmed PY - 2012/2/15/medline SP - 6387 EP - 91 JF - Blood JO - Blood VL - 118 IS - 24 N2 - 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. SN - 1528-0020 UR - https://www.unboundmedicine.com/medline/citation/22031859/IPH2101_a_novel_anti_inhibitory_KIR_antibody_and_lenalidomide_combine_to_enhance_the_natural_killer_cell_versus_multiple_myeloma_effect_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=22031859 DB - PRIME DP - Unbound Medicine ER -