The lymphoid cell surface receptor NTB-A: A novel monoclonal antibody target for leukaemia and lymphoma therapeutics

Wouter Korver; Shweta Singh; Shouchun Liu; Xiaoxian Zhao; Shirlee Yonkovich; Allison Sweeney; Kristin Anton; Woodrow E. Lomas; Rachel Greenwood; Ashley Smith; Denise Hoang Tran; Pauline Shinkawa; Mark Jimenez; Patricia Yeung; Gerard Aguilar; Servando Palencia; Paolo Vatta; Matthew Mueller; Xiaoming Zhan; Elizabeth M. Newton; Yi Liu; Jingsong Zhao; Peter Emtage; Michael D. Levy; Eric D. Hsi; Walter D. Funk; Arie Abo

doi:10.1111/j.1365-2141.2007.06569.x

The lymphoid cell surface receptor NTB-A: A novel monoclonal antibody target for leukaemia and lymphoma therapeutics

Wouter Korver, Shweta Singh, Shouchun Liu, Xiaoxian Zhao, Shirlee Yonkovich, Allison Sweeney, Kristin Anton, Woodrow E. Lomas, Rachel Greenwood, Ashley Smith, Denise Hoang Tran, Pauline Shinkawa, Mark Jimenez, Patricia Yeung, Gerard Aguilar, Servando Palencia, Paolo Vatta, Matthew Mueller, Xiaoming Zhan, Elizabeth M. NewtonYi Liu, Jingsong Zhao, Peter Emtage, Michael D. Levy, Eric D. Hsi, Walter D. Funk, Arie Abo

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.

Original language	English (US)
Pages (from-to)	307-318
Number of pages	12
Journal	British Journal of Haematology
Volume	137
Issue number	4
DOIs	https://doi.org/10.1111/j.1365-2141.2007.06569.x
State	Published - May 1 2007

Keywords

Chronic lymphocytic leukaemia
Immunotherapy
Leukaemia
Lymphoma
Monoclonal antibody

ASJC Scopus subject areas

Hematology

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10.1111/j.1365-2141.2007.06569.x

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Korver, W., Singh, S., Liu, S., Zhao, X., Yonkovich, S., Sweeney, A., Anton, K., Lomas, W. E., Greenwood, R., Smith, A., Tran, D. H., Shinkawa, P., Jimenez, M., Yeung, P., Aguilar, G., Palencia, S., Vatta, P., Mueller, M., Zhan, X., ... Abo, A. (2007). The lymphoid cell surface receptor NTB-A: A novel monoclonal antibody target for leukaemia and lymphoma therapeutics. British Journal of Haematology, 137(4), 307-318. https://doi.org/10.1111/j.1365-2141.2007.06569.x

Korver, W, Singh, S, Liu, S, Zhao, X, Yonkovich, S, Sweeney, A, Anton, K, Lomas, WE, Greenwood, R, Smith, A, Tran, DH, Shinkawa, P, Jimenez, M, Yeung, P, Aguilar, G, Palencia, S, Vatta, P, Mueller, M, Zhan, X, Newton, EM, Liu, Y, Zhao, J, Emtage, P, Levy, MD, Hsi, ED, Funk, WD & Abo, A 2007, 'The lymphoid cell surface receptor NTB-A: A novel monoclonal antibody target for leukaemia and lymphoma therapeutics', British Journal of Haematology, vol. 137, no. 4, pp. 307-318. https://doi.org/10.1111/j.1365-2141.2007.06569.x

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abstract = "NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.",

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AU - Korver, Wouter

AU - Singh, Shweta

AU - Liu, Shouchun

AU - Zhao, Xiaoxian

AU - Yonkovich, Shirlee

AU - Sweeney, Allison

AU - Anton, Kristin

AU - Lomas, Woodrow E.

AU - Greenwood, Rachel

AU - Smith, Ashley

AU - Tran, Denise Hoang

AU - Shinkawa, Pauline

AU - Jimenez, Mark

AU - Yeung, Patricia

AU - Aguilar, Gerard

AU - Palencia, Servando

AU - Vatta, Paolo

AU - Mueller, Matthew

AU - Zhan, Xiaoming

AU - Newton, Elizabeth M.

AU - Liu, Yi

AU - Zhao, Jingsong

AU - Emtage, Peter

AU - Levy, Michael D.

AU - Hsi, Eric D.

AU - Funk, Walter D.

AU - Abo, Arie

PY - 2007/5/1

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N2 - NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.

AB - NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.

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KW - Immunotherapy

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KW - Lymphoma

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ER -

The lymphoid cell surface receptor NTB-A: A novel monoclonal antibody target for leukaemia and lymphoma therapeutics

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