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IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers.
Curr Opin Mol Ther 2010; 12(6):724-33CO

Abstract

NK-cell activity against tumor cells is regulated by a complex balance of inhibitory and activating signals, which are mediated by the binding of NK-cell receptors to activating and inhibitory ligands expressed on tumor cells. Thus, the disruption of the inhibitory cascade would shift the balance to activation. IPH-2101 (1-7F9), being developed by Innate Pharma, is a fully human IgG4 anti-killer immunoglobulin-like receptor (KIR) mAb for the treatment of hematological malignancies, such as acute myeloid leukemia (AML) and multiple myeloma (MM). In preclinical studies, IPH-2101 selectively bound to KIR2DL1, 2 and 3, and KIR2DS1 and 2, and exposure of KIR-transfected target cell lines to IPH-2101 led to an augmented NK-cell-mediated lysis. In phase I clinical trials in patients with AML and MM treated with IPH-2101, activation of NK cells was observed and IPH-2101 exhibited a good safety profile. At the time of publication, patients with MM had been recruited to phase II clinical trials to assess single-agent IPH-2101 or IPH-2101 in combination with lenalidomide. These and larger, randomized trials are warranted to clarify whether enhancing a patient's NK-cell activity by IPH-2101 will be a viable approach in the treatment of hematological malignancies.

Authors+Show Affiliations

Karolinska Institutet, Karolinska University Hospital Huddinge, Department of Medicine, SE-14186 Stockholm, Sweden. Evren.Alici@ki.se

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21154164

Citation

Alici, Evren. "IPH-2101, a Fully Human anti-NK-cell Inhibitory Receptor mAb for the Potential Treatment of Hematological Cancers." Current Opinion in Molecular Therapeutics, vol. 12, no. 6, 2010, pp. 724-33.
Alici E. IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. Curr Opin Mol Ther. 2010;12(6):724-33.
Alici, E. (2010). IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. Current Opinion in Molecular Therapeutics, 12(6), pp. 724-33.
Alici E. IPH-2101, a Fully Human anti-NK-cell Inhibitory Receptor mAb for the Potential Treatment of Hematological Cancers. Curr Opin Mol Ther. 2010;12(6):724-33. PubMed PMID: 21154164.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. A1 - Alici,Evren, PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2011/5/20/medline SP - 724 EP - 33 JF - Current opinion in molecular therapeutics JO - Curr. Opin. Mol. Ther. VL - 12 IS - 6 N2 - NK-cell activity against tumor cells is regulated by a complex balance of inhibitory and activating signals, which are mediated by the binding of NK-cell receptors to activating and inhibitory ligands expressed on tumor cells. Thus, the disruption of the inhibitory cascade would shift the balance to activation. IPH-2101 (1-7F9), being developed by Innate Pharma, is a fully human IgG4 anti-killer immunoglobulin-like receptor (KIR) mAb for the treatment of hematological malignancies, such as acute myeloid leukemia (AML) and multiple myeloma (MM). In preclinical studies, IPH-2101 selectively bound to KIR2DL1, 2 and 3, and KIR2DS1 and 2, and exposure of KIR-transfected target cell lines to IPH-2101 led to an augmented NK-cell-mediated lysis. In phase I clinical trials in patients with AML and MM treated with IPH-2101, activation of NK cells was observed and IPH-2101 exhibited a good safety profile. At the time of publication, patients with MM had been recruited to phase II clinical trials to assess single-agent IPH-2101 or IPH-2101 in combination with lenalidomide. These and larger, randomized trials are warranted to clarify whether enhancing a patient's NK-cell activity by IPH-2101 will be a viable approach in the treatment of hematological malignancies. SN - 2040-3445 UR - https://www.unboundmedicine.com/medline/citation/21154164/IPH-2101,_a_fully_human_anti-NK-cell_inhibitory_receptor_mAb_for_the_potential_treatment_of_hematological_cancers L2 - https://medlineplus.gov/multiplemyeloma.html DB - PRIME DP - Unbound Medicine ER -