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IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers.

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.

Links

Authors+Show Affiliations

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

Source

MeSH

Acute Disease
Antibodies, Monoclonal
Clinical Trials as Topic
Humans
Killer Cells, Natural
Leukemia, Myeloid
Multiple Myeloma
Protein Binding
Receptors, KIR
Receptors, Natural Killer Cell

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 -