Howard D R, Eaves A C, Takei F
Cancer Res. 1985 Dec;45(12 Pt 1):6322-7.
The non-Hodgkin's lymphomas are a clinically, morphologically, and immunologically heterogeneous group of diseases. Why lymphoma cells are unresponsive to normal regulatory growth controls and how they differ from normal lymphocytes are not well understood. In order to address these questions we have raised monoclonal antibodies to neoplastic B-cells. Two of these, LM-26 and LM-155, show a high degree of specificity for B-cell lymphomas. When tested by fluorescence activated cell sorter analysis, LM-26 reacted with 80% (18 of 23) of B-cell lymphomas freshly explanted from patients and LM-155 reacted with 20% (5 of 23). The antigenic determinant detected by LM-26 was also found to be present on four of seven neoplastic large cell B-lymphoma lines. LM-155 detected a determinant present on all seven of these lines. For neither monoclonal antibody was there any association between antibody reactivity and the morphological subtype of lymphoma examined or the type of cell surface immunoglobulin expressed. LM-155 reacted with one case of B-cell acute lymphoblastic leukemia. Neither antibody reacted with normal B-cell blasts, normal peripheral blood mononuclear or marrow cells, T-cell leukemias or lymphomas, or chronic lymphocytic leukemia cells. Lymphocytes from reactive lymphoid hyperplasias involving lymph nodes, spleen, peripheral blood, and lung were also negative for LM-26 and LM-155 binding or showed only a small percentage of cells positive (4-8%). Both monoclonals were unreactive with non-B-lymphoid neoplastic cell lines, nine of ten Epstein-Barr virus transformed B-cell lines, and cells freshly explanted from patients with cancers of diverse cellular origins. Fluorescence activated cell sorter analysis of the expression of the antigens defined by LM-26 and LM-155 on lymphoma cells and normal B-cell blasts suggests that they are not normal differentiation antigens associated with lymphocyte activation or proliferation. The highly restricted expression of detectable levels of antigens reactive with monoclonal antibodies LM-26 and LM-155 on non-Hodgkin's lymphoma cells suggests a possible relation to their neoplastic properties. From a practical viewpoint these monoclonals may prove useful in the diagnosis, classification, detection of residual disease, and treatment of the non-Hodgkin's lymphomas.
非霍奇金淋巴瘤是一组在临床、形态学和免疫学上具有异质性的疾病。淋巴瘤细胞为何对正常的调节性生长控制无反应,以及它们与正常淋巴细胞有何不同,目前尚不清楚。为了解决这些问题,我们制备了针对肿瘤性B细胞的单克隆抗体。其中两种,即LM - 26和LM - 155,对B细胞淋巴瘤表现出高度特异性。通过荧光激活细胞分选分析检测,LM - 26与80%(23例中的18例)从患者体内新鲜分离出的B细胞淋巴瘤发生反应,而LM - 155与20%(23例中的5例)发生反应。还发现LM - 26检测到的抗原决定簇存在于7株肿瘤性大细胞B淋巴瘤细胞系中的4株上。LM - 155检测到该决定簇存在于所有这7株细胞系上。对于这两种单克隆抗体,抗体反应性与所检测淋巴瘤的形态学亚型或细胞表面免疫球蛋白的表达类型之间均无关联。LM - 155与1例B细胞急性淋巴细胞白血病发生反应。两种抗体均不与正常B细胞母细胞、正常外周血单核细胞或骨髓细胞、T细胞白血病或淋巴瘤或慢性淋巴细胞白血病细胞发生反应。涉及淋巴结、脾脏、外周血和肺的反应性淋巴组织增生中的淋巴细胞对LM - 26和LM - 155结合也呈阴性,或仅显示一小部分细胞呈阳性(4 - 8%)。两种单克隆抗体均不与非B淋巴细胞肿瘤细胞系、10株爱泼斯坦 - 巴尔病毒转化的B细胞系中的9株以及来自不同细胞起源癌症患者的新鲜分离细胞发生反应。对淋巴瘤细胞和正常B细胞母细胞上由LM - 26和LM - 155定义的抗原表达进行荧光激活细胞分选分析表明,它们不是与淋巴细胞活化或增殖相关的正常分化抗原。在非霍奇金淋巴瘤细胞上与单克隆抗体LM - 26和LM - 155反应的可检测水平抗原的高度受限表达表明其可能与肿瘤特性有关。从实际应用的角度来看,这些单克隆抗体可能在非霍奇金淋巴瘤的诊断、分类、残留疾病检测及治疗中发挥作用。