淋巴样细胞表面受体NTB-A：白血病和淋巴瘤治疗的新型单克隆抗体靶点。

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

作者信息

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

机构信息

Nuvelo, Inc., San Carlos, CA, USA.

出版信息

Br J Haematol. 2007 May;137(4):307-18. doi: 10.1111/j.1365-2141.2007.06569.x.

DOI:10.1111/j.1365-2141.2007.06569.x

PMID:17456053

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.

摘要

NTB-A是一种与CD2相关的细胞表面蛋白，主要在包括慢性淋巴细胞白血病（CLL）和淋巴瘤患者的B淋巴细胞在内的淋巴细胞上表达。我们已经制备了一系列针对NTB-A的单克隆抗体（mAb），并评估了它们对CLL的治疗潜力。针对NTB-A的选择性单克隆抗体在细胞系以及从CLL患者新鲜分离的B淋巴细胞中进行了功能补体依赖性细胞毒性（CDC）和抗体依赖性细胞毒性（ADCC）试验。虽然在T细胞和自然杀伤（NK）细胞中检测到较低水平的NTB-A，但CDC活性主要在从CLL患者分离的B细胞和B淋巴瘤细胞系中表现出来。通过小干扰RNA在靶细胞中敲低NTB-A会导致较低的细胞毒性，证明了单克隆抗体的特异性。此外，抗NTB-A单克隆抗体在裸鼠中对CA46人淋巴瘤异种移植物以及在严重联合免疫缺陷小鼠中对全身播散的Raji人淋巴瘤细胞表现出抗肿瘤活性。综上所述，这些结果表明NTB-A是白血病和淋巴瘤免疫治疗的潜在新靶点。