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 journalArticle

11 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)307-318
Number of pages12
JournalBritish Journal of Haematology
Volume137
Issue number4
DOIs
StatePublished - May 2007

Fingerprint

Cell Surface Receptors
B-Cell Chronic Lymphocytic Leukemia
Lymphoma
Leukemia
Monoclonal Antibodies
Lymphocytes
B-Lymphocytes
Therapeutics
Cell Line
Natural Killer T-Cells
SCID Mice
Heterografts
Nude Mice
Immunotherapy
Small Interfering RNA
Membrane Proteins
Antibodies
Neoplasms

Keywords

  • Chronic lymphocytic leukaemia
  • Immunotherapy
  • Leukaemia
  • Lymphoma
  • Monoclonal antibody

ASJC Scopus subject areas

  • Hematology

Cite this

The lymphoid cell surface receptor NTB-A : A novel monoclonal antibody target for leukaemia and lymphoma therapeutics. / Korver, Wouter; Singh, Shweta; Liu, Shouchun; Zhao, Xiaoxian; Yonkovich, Shirlee; Sweeney, Allison; Anton, Kristin; Lomas, Woodrow E.; Greenwood, Rachel; Smith, Ashley; Tran, Denise Hoang; Shinkawa, Pauline; Jimenez, Mark; Yeung, Patricia; Aguilar, Gerard; Palencia, Servando; Vatta, Paolo; Mueller, Matthew; Zhan, Xiaoming; Newton, Elizabeth M.; Liu, Yi; Zhao, Jingsong; Emtage, Peter; Levy, Michael D.; Hsi, Eric D.; Funk, Walter D.; Abo, Arie.

In: British Journal of Haematology, Vol. 137, No. 4, 05.2007, p. 307-318.

Research output: Contribution to journalArticle

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
Korver, Wouter ; Singh, Shweta ; Liu, Shouchun ; Zhao, Xiaoxian ; Yonkovich, Shirlee ; Sweeney, Allison ; Anton, Kristin ; Lomas, Woodrow E. ; Greenwood, Rachel ; Smith, Ashley ; Tran, Denise Hoang ; Shinkawa, Pauline ; Jimenez, Mark ; Yeung, Patricia ; Aguilar, Gerard ; Palencia, Servando ; Vatta, Paolo ; Mueller, Matthew ; Zhan, Xiaoming ; Newton, Elizabeth M. ; Liu, Yi ; Zhao, Jingsong ; Emtage, Peter ; Levy, Michael D. ; Hsi, Eric D. ; Funk, Walter D. ; Abo, Arie. / The lymphoid cell surface receptor NTB-A : A novel monoclonal antibody target for leukaemia and lymphoma therapeutics. In: British Journal of Haematology. 2007 ; Vol. 137, No. 4. pp. 307-318.
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AU - Sweeney, Allison

AU - Anton, Kristin

AU - Lomas, Woodrow E.

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AU - Zhan, Xiaoming

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AU - Liu, Yi

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