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

Abstract

Summary 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.

Expression of SLAM (CD150) cell-surface receptors on human B-cell subsets: From pro-B to plasma cells

“…The highest expression levels are detected on B cells from leukemic and lymphoma patients [50][51][52]. It is also expressed on eosinophils and to a weaker extent on monocytes, but not on macrophages, basophils, granulocytes, or neutrophils [45,50,51,53]. Lymphoid tissues such as spleen, thymus, and lymph nodes present this receptor to a high degree, while low expression levels are detected in bone marrow, lung, and liver [50].…”

New B-cell CD molecules

“…CD352 plays an important role in NK cells not only by enhancing cytokine secretion and proliferation, but also by modulating CD8 + T and NK cells cytotoxicity [25]. It should be noted that, CD352 is a potential target for leukemia and lymphoma therapeutics since anti-CD352 mAbs have been described as mediating anti-tumor activities against lymphoma cells without affecting samples from healthy donors [27]. However, this possibility has to be carefully evaluated since CD352 is highly expressed on most leukocytes.…”

Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia

“…Details of the staining process have been described elsewhere. 19 Blasts were gated based on low side scatter versus CD45 dim expression. A sample was considered positive for CLL-1 or CD33 if the ratio of the geometric mean fluorescence intensity (MFI) of the stained sample and that of isoform IgG control was greater than two and more than 20% of the cells expressed the antigen compared with the control sample.…”