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Br J Dermatol. 2016 Aug;175(2):325-33. doi: 10.1111/bjd.14626. Epub 2016 Jul 13.

KIR3DL2 (CD158k) is a potential therapeutic target in primary cutaneous anaplastic large-cell lymphoma.

Author information

1
Département de Pathologie, AP-HP, Hôpital Saint-Louis, Paris, 75010, France.
2
Université Paris-Diderot, Sorbonne Paris Cité, Paris, 75010, France.
3
INSERM U1165, Paris, F-75010, France.
4
INSERM U976, Centre de Recherche en Dermatologie, Paris, 75010, France.
5
Innate Pharma, Marseille, F-13276, France.
6
Département de Dermatologie, AP-HP, Hôpital Saint-Louis, Paris, 75010, France.
7
Roger Williams Medical Center, Providence, RI, U.S.A.
8
Boston University, Boston, MA, U.S.A.

Abstract

BACKGROUND:

KIR3DL2, an inhibitory receptor expressed by natural killer cells and a subset of normal CD8(+) T cells, is aberrantly expressed in neoplastic cells in transformed mycosis fungoides and Sézary syndrome. Anti-KIR3DL2 targeted antibody therapy has shown potent activity in preclinical models for these diseases.

OBJECTIVES:

To examine the expression of KIR3DL2 and its potential use as a therapeutic target in patients with primary cutaneous anaplastic large-cell lymphoma (pcALCL), the most aggressive cutaneous CD30(+) lymphoproliferative disease.

METHODS:

Samples from 11 patients with pcALCL and three CD30(+) lymphoproliferative disease cell lines - Mac1, Mac2a and Mac2b - were used in KIR3DL2 expression studies using immunohistochemistry, flow cytometry and reverse-transcriptase quantitative polymerase chain reaction. The effect of IPH4102, a monoclonal humanized IgG1 targeting KIR3DL2, was assessed by in vitro cytotoxicity assays against Mac1, Mac2a and Mac2b using allogeneic peripheral blood mononuclear cells as effectors.

RESULTS:

KIR3DL2 mRNA and protein were found in all human samples of pcALCL, and in the Mac2a and Mac2b cell lines. KIR3DL2 protein expression was present on 85·8 ± 14·0% of CD30(+) skin-infiltrating tumour cells. In vitro functional studies showed that KIR3DL2(+) Mac2a and Mac2b pcALCL lines are sensitive to antibody-derived cytotoxicity mediated by IPH4102, through activation of natural killer cells, in a concentration-dependent manner.

CONCLUSIONS:

pcALCL tumour cells express KIR3DL2, and we provide preclinical proof of concept for the use of IPH4102, a humanized anti-KIR3DL2 antibody, to treat patients with primary cutaneous CD30(+) ALCL.

PMID:
27037558
DOI:
10.1111/bjd.14626
[Indexed for MEDLINE]

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