Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies

Holbrook E. Kohrt; Ariane Thielens; Aurelien Marabelle; Idit Sagiv-Barfi; Caroline Sola; Fabien Chanuc; Nicolas Fuseri; Cécile Bonnafous; Debra Czerwinski; Amanda Rajapaksa; Erin Waller; Sophie Ugolini; Eric Vivier; François Romagné; Ronald Levy; Mathieu Bléry; Pascale André

doi:10.1182/Blood-2013-08-519199

Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies

Holbrook E. Kohrt, Ariane Thielens, Aurelien Marabelle, Idit Sagiv-Barfi, Caroline Sola, Fabien Chanuc, Nicolas Fuseri, Cécile Bonnafous, Debra Czerwinski, Amanda Rajapaksa, Erin Waller, Sophie Ugolini, Eric Vivier, François Romagné, Ronald Levy, Mathieu Bléry, Pascale André

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Résumé

Natural killer (NK) cells mediate antilymphoma activity by spontaneous cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when triggered by rituximab, an anti- CD20monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. The balance of inhibitory and activating signals determines the magnitude of the efficacy of NK cells by spontaneous cytotoxicity. Here, using a killer-cell immunoglobulin-like receptor (KIR) transgenic murine model, we show that blockade of the interface of inhibitory KIRs with major histocompatibility complex (MHC) class I antigens on lymphoma cells by anti-KIR antibodies prevents a tolerogenic interaction and augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces enhanced NKcell- mediated, rituximab-dependent cytotoxicity against lymphoma in vitro and in vivo in KIR transgenic and syngeneic murine lymphomamodels. These results support a therapeutic strategy of combination rituximab and KIR blockade through lirilumab, illustrating the potential efficacy of combining a tumor-targeting therapy with an NK-cell agonist, thus stimulating the postrituximab antilymphoma immune response. (Blood. 2014;123(5):678-686).

langue originale	Anglais
Pages (de - à)	678-686
Nombre de pages	9
journal	Blood
Volume	123
Numéro de publication	5
Les DOIs	https://doi.org/10.1182/Blood-2013-08-519199
état	Publié - 30 janv. 2014
Modification externe	Oui

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10.1182/Blood-2013-08-519199

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Kohrt, H. E., Thielens, A., Marabelle, A., Sagiv-Barfi, I., Sola, C., Chanuc, F., Fuseri, N., Bonnafous, C., Czerwinski, D., Rajapaksa, A., Waller, E., Ugolini, S., Vivier, E., Romagné, F., Levy, R., Bléry, M., & André, P. (2014). Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood, 123(5), 678-686. https://doi.org/10.1182/Blood-2013-08-519199

@article{2ccf905c3ee94ebcb8157fc863889c13,

title = "Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies",

abstract = "Natural killer (NK) cells mediate antilymphoma activity by spontaneous cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when triggered by rituximab, an anti- CD20monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. The balance of inhibitory and activating signals determines the magnitude of the efficacy of NK cells by spontaneous cytotoxicity. Here, using a killer-cell immunoglobulin-like receptor (KIR) transgenic murine model, we show that blockade of the interface of inhibitory KIRs with major histocompatibility complex (MHC) class I antigens on lymphoma cells by anti-KIR antibodies prevents a tolerogenic interaction and augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces enhanced NKcell- mediated, rituximab-dependent cytotoxicity against lymphoma in vitro and in vivo in KIR transgenic and syngeneic murine lymphomamodels. These results support a therapeutic strategy of combination rituximab and KIR blockade through lirilumab, illustrating the potential efficacy of combining a tumor-targeting therapy with an NK-cell agonist, thus stimulating the postrituximab antilymphoma immune response. (Blood. 2014;123(5):678-686).",

author = "Kohrt, {Holbrook E.} and Ariane Thielens and Aurelien Marabelle and Idit Sagiv-Barfi and Caroline Sola and Fabien Chanuc and Nicolas Fuseri and C{\'e}cile Bonnafous and Debra Czerwinski and Amanda Rajapaksa and Erin Waller and Sophie Ugolini and Eric Vivier and Fran{\c c}ois Romagn{\'e} and Ronald Levy and Mathieu Bl{\'e}ry and Pascale Andr{\'e}",

year = "2014",

month = jan,

day = "30",

doi = "10.1182/Blood-2013-08-519199",

language = "English",

volume = "123",

pages = "678--686",

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Kohrt, HE, Thielens, A, Marabelle, A, Sagiv-Barfi, I, Sola, C, Chanuc, F, Fuseri, N, Bonnafous, C, Czerwinski, D, Rajapaksa, A, Waller, E, Ugolini, S, Vivier, E, Romagné, F, Levy, R, Bléry, M & André, P 2014, 'Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies', Blood, VOL. 123, Numéro 5, p. 678-686. https://doi.org/10.1182/Blood-2013-08-519199

TY - JOUR

T1 - Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies

AU - Kohrt, Holbrook E.

AU - Thielens, Ariane

AU - Marabelle, Aurelien

AU - Sagiv-Barfi, Idit

AU - Sola, Caroline

AU - Chanuc, Fabien

AU - Fuseri, Nicolas

AU - Bonnafous, Cécile

AU - Czerwinski, Debra

AU - Rajapaksa, Amanda

AU - Waller, Erin

AU - Ugolini, Sophie

AU - Vivier, Eric

AU - Romagné, François

AU - Levy, Ronald

AU - Bléry, Mathieu

AU - André, Pascale

PY - 2014/1/30

Y1 - 2014/1/30

N2 - Natural killer (NK) cells mediate antilymphoma activity by spontaneous cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when triggered by rituximab, an anti- CD20monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. The balance of inhibitory and activating signals determines the magnitude of the efficacy of NK cells by spontaneous cytotoxicity. Here, using a killer-cell immunoglobulin-like receptor (KIR) transgenic murine model, we show that blockade of the interface of inhibitory KIRs with major histocompatibility complex (MHC) class I antigens on lymphoma cells by anti-KIR antibodies prevents a tolerogenic interaction and augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces enhanced NKcell- mediated, rituximab-dependent cytotoxicity against lymphoma in vitro and in vivo in KIR transgenic and syngeneic murine lymphomamodels. These results support a therapeutic strategy of combination rituximab and KIR blockade through lirilumab, illustrating the potential efficacy of combining a tumor-targeting therapy with an NK-cell agonist, thus stimulating the postrituximab antilymphoma immune response. (Blood. 2014;123(5):678-686).

AB - Natural killer (NK) cells mediate antilymphoma activity by spontaneous cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when triggered by rituximab, an anti- CD20monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. The balance of inhibitory and activating signals determines the magnitude of the efficacy of NK cells by spontaneous cytotoxicity. Here, using a killer-cell immunoglobulin-like receptor (KIR) transgenic murine model, we show that blockade of the interface of inhibitory KIRs with major histocompatibility complex (MHC) class I antigens on lymphoma cells by anti-KIR antibodies prevents a tolerogenic interaction and augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces enhanced NKcell- mediated, rituximab-dependent cytotoxicity against lymphoma in vitro and in vivo in KIR transgenic and syngeneic murine lymphomamodels. These results support a therapeutic strategy of combination rituximab and KIR blockade through lirilumab, illustrating the potential efficacy of combining a tumor-targeting therapy with an NK-cell agonist, thus stimulating the postrituximab antilymphoma immune response. (Blood. 2014;123(5):678-686).

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U2 - 10.1182/Blood-2013-08-519199

DO - 10.1182/Blood-2013-08-519199

M3 - Article

C2 - 24326534

AN - SCOPUS:84894030202

SN - 0006-4971

VL - 123

SP - 678

EP - 686

JO - Blood

JF - Blood

IS - 5

ER -