Anti-human tumor antibodies induced in mice and rabbits by "internal image" anti-idiotypic monoclonal immunoglobulins.
Anti-human tumor antibodies induced in mice and rabbits by "internal image" anti-idiotypic monoclonal immunoglobulins.
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通过“内部图像”抗独特型单克隆免疫球蛋白在小鼠和兔子中诱导抗人肿瘤抗体。
作者：
G. Viale;F. Grassi;M. Pelagi;R. Alzani;S. Ménard;S. Miotti;R. Buffa;A. Gini;A. Siccardi
MBr1 是一种鼠单克隆抗体，定义了存在于乳腺癌细胞系 MCF-7 上的人类组织特异性肿瘤相关球苷的糖表位 [CaMBr1]。正常和肿瘤性乳腺上皮细胞上的糖蛋白以及某些卵巢囊肿液中的粘蛋白具有相同的表位。我们在独特型免疫序列中使用MBr1作为单克隆抗肿瘤抗体，以获得和表征原始表位的“内部图像”，以用作血清学免疫测定中标称抗原的替代品。获得了两种单克隆抗独特型抗体（β-1和β-2），它们与MBr1上互补位相关的独特位发生反应。通过“抗原”和“抗体”竞争测定对这些分子的抗原和免疫原性特性的分析提供了证据，证明β-1和β-2都具有MBr1定义的表位的“内部图像”。此外，当注射到小鼠和兔子体内时，β-1和β-2都会诱导产生抗抗独特型抗体，该抗体在结合MCF-7以及正常和肿瘤性乳腺上皮细胞方面模仿MBr1。这些数据在肿瘤相关抗原替代品生产中的可能应用及其在血清学免疫测定中的应用进行了讨论。
MBr1 is a murine monoclonal antibody, defining a saccharidic epitope [CaMBr1] of a human tissue-specific, tumor-associated globoside, present on the mammary carcinoma cell line MCF-7. The same epitope is shared by glycoproteins present on normal and neoplastic mammary epithelial cells, and by mucins from some ovarian cyst fluids. We have used MBr1 as the monoclonal antitumor antibody in an idiotypic sequence of immunizations in order to obtain and characterize "internal images" of the original epitope to be used as substitutes of the nominal antigen in serologic immunoassays. Two monoclonal anti-idiotypic antibodies (beta-1 and beta-2), which reacted with paratope-related idiotopes on MBr1, were obtained. The analysis of the antigenic and immunogenic properties of these molecules by both "antigen" and "antibody" competition assays provided evidence that both beta-1 and beta-2 bear "internal images" of the MBr1-defined epitope. Moreover, when injected in mice and rabbits both beta-1 and beta-2 induced anti anti-idiotypic antibodies, which mimicked MBr1 in binding MCF-7 as well as normal and neoplastic mammary gland epithelial cells. These data are discussed in terms of their possible application to the production of tumor-associated antigen substitutes and their use in serologic immunoassays.