Zhou Minglong, Fadlelmola Faisal M, Cohn Jason B, Skinnider Brian, Gascoyne Randy D, Banerjee Diponkar
Centre for Translational and Applied Genomics (CTAG), Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver Cancer Centre, BC V5Z 4E6, Canada.
Mol Cancer. 2008 Jan 24;7:12. doi: 10.1186/1476-4598-7-12.
CD30, a 120 kDa surface phosphorylated protein is a member of tumour necrosis/nerve growth factor receptor (TNF/NGFR) family and constitutively expressed by Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) and the neoplastic cells of Anaplastic Large Cell Lymphoma (ALCL). A disease-specific protein marker is yet to be identified in Hodgkin lymphoma cells. In order to define HL-specific biomarkers, novel murine monoclonal antibodies were developed in our laboratory.
Murine monoclonal antibodies (mabs) were raised against the B3 sub clone of HL-derived cell line KM-H2. Two of these mabs (clone R23.1 mab and clone R24.1 mab) are IgG1 class antibodies that recognize a 21 kDa protein present at the cell membrane and in the cytoplasm in HL-derived cell lines. Clone R24.1 mab recognizes a formalin-resistant epitope and labels HRS cells in tissue samples from patients with HL of the classical type, ALCL, and subsets of T and B cell aggressive Non-Hodgkin Lymphomas (NHL). The antigen recognized by the clone R23.1 mab and clone R24.1 mab does not share epitopes with CD30 cluster regions A, B, or C, and, unlike CD30, is not expressed by phytohemagglutinin (PHA) activated T cells.
The 21 kDa protein detected by clone R23.1 and clone R24.1 mabs is a novel membrane-associated protein that may be a potential marker for the diagnosis and targeted therapy of HL and aggressive T and B cell NHL.
CD30是一种120 kDa的表面磷酸化蛋白,属于肿瘤坏死/神经生长因子受体(TNF/NGFR)家族,在霍奇金淋巴瘤(HL)的霍奇金和里德-斯腾伯格(HRS)细胞以及间变性大细胞淋巴瘤(ALCL)的肿瘤细胞中组成性表达。在霍奇金淋巴瘤细胞中尚未鉴定出疾病特异性蛋白标志物。为了确定HL特异性生物标志物,我们实验室开发了新型鼠单克隆抗体。
针对HL衍生细胞系KM-H2的B3亚克隆产生了鼠单克隆抗体(mabs)。其中两种单克隆抗体(克隆R23.1 mab和克隆R24.1 mab)是IgG1类抗体,可识别HL衍生细胞系细胞膜和细胞质中存在的一种21 kDa蛋白。克隆R24.1 mab识别一种福尔马林抗性表位,并标记经典型HL、ALCL以及T和B细胞侵袭性非霍奇金淋巴瘤(NHL)亚组患者组织样本中的HRS细胞。克隆R23.1 mab和克隆R24.1 mab识别的抗原与CD30簇区域A、B或C不共享表位,并且与CD30不同,不被植物血凝素(PHA)激活的T细胞表达。
克隆R23.1和克隆R24.1 mabs检测到的21 kDa蛋白是一种新型膜相关蛋白,可能是HL以及侵袭性T和B细胞NHL诊断和靶向治疗的潜在标志物。