Giardina S L, Schroff R W, Kipps T J, Woodhouse C S, Abrams P G, Rager H C, Morgan A C, Foon K A
J Immunol. 1985 Jul;135(1):653-8.
We developed murine anti-idiotype monoclonal antibodies for each of four patients with B cell-derived leukemias and lymphomas. Idiotypic immunoglobulin was isolated from mouse X human tumor-cell hybridomas or from patients' serum and was used to immunize mice for the development of murine anti-idiotype monoclonal antibodies. Each patient's anti-idiotype antibodies demonstrated reactivity restricted to the immunizing immunoglobulin, thereby limiting their therapeutic utility to a single individual. In addition, we isolated isotype switch variants of hybridomas producing monoclonal anti-idiotypic antibody. The restricted specificity of these antibodies was found to be of value for the analysis of the extent of malignant B cell infiltration in a variety of tissues from several patients. Large populations of idiotype-bearing cells were detectable in biopsy specimens from patients K.T. and L.H. In contrast, although bone marrow specimens from patient G.D. were apparently devoid of morphologically abnormal cells, a small, highly fluorescent population of cells was demonstrable underscoring the potential utility of these antibodies for posttreatment evaluation as well as for therapy. In a fourth patient, H.M., anti-idiotype antibodies developed against the circulating macroglobulin isolated from his plasma failed to react with either his circulating or bone marrow hairy cell leukemia cells. However, examination of an enlarged inguinal lymph node revealed the presence of a large number of idiotype-bearing cells. Thus, the presence of two distinct malignant B cell clones were discovered in this individual through the use of anti-idiotype monoclonal antibodies. Anti-idiotype antibodies, therefore, represent a highly specific tool for the evaluation and potential therapy of B cell malignancies in individual patients.
我们为4例B细胞来源的白血病和淋巴瘤患者分别制备了鼠抗独特型单克隆抗体。独特型免疫球蛋白从小鼠X人肿瘤细胞杂交瘤或患者血清中分离出来，用于免疫小鼠以制备鼠抗独特型单克隆抗体。每位患者的抗独特型抗体显示出仅与免疫用免疫球蛋白发生反应，从而将其治疗用途局限于单个个体。此外，我们分离了产生单克隆抗独特型抗体的杂交瘤的同种型转换变体。发现这些抗体的特异性受限对于分析来自数例患者的多种组织中恶性B细胞浸润程度具有价值。在患者K.T.和L.H.的活检标本中可检测到大量带有独特型的细胞。相比之下，尽管患者G.D.的骨髓标本明显没有形态异常的细胞，但仍可显示出一小群高荧光细胞，这突出了这些抗体在治疗后评估以及治疗中的潜在用途。在第四例患者H.M.中，针对从其血浆中分离出的循环巨球蛋白产生的抗独特型抗体与他的循环或骨髓毛细胞白血病细胞均无反应。然而，对一个肿大的腹股沟淋巴结检查发现存在大量带有独特型的细胞。因此，通过使用抗独特型单克隆抗体在该个体中发现了两个不同的恶性B细胞克隆。因此，抗独特型抗体是评估和潜在治疗个体患者B细胞恶性肿瘤的高度特异性工具。
