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使用抗癌胚抗原抗体的抗独特型单克隆抗体诱导抗原特异性免疫反应。

Induction of antigen-specific immune response with use of anti-idiotypic monoclonal antibodies to anti-carcinoembryonic antigen antibodies.

作者信息

Tsujisaki M, Imai K, Tokuchi S, Hanzawa Y, Ishida T, Kitagawa H, Hinoda Y, Yachi A

机构信息

Department of Internal Medicine (Section 1), Sapporo Medical College, Japan.

出版信息

Cancer Res. 1991 May 15;51(10):2599-604.

PMID:2021940
Abstract

Anti-idiotypic monoclonal antibodies (MoAbs) were prepared in a syngeneic system against anti-carcinoembryonic antigen (CEA) MoAb 5B3 (IgG1), which reacted with a carbohydrate moiety on CEA, and MoAb MA208 (IgG1), which reacted with a peptide on CEA. Anti-idiotypic MoAb T3-503 and T4-202 recognized the private idiotype of MoAb 5B3; anti-idiotypic MoAb M7-049 and M7-625 did so for MoAb MA208. Idiotype mapping showed that MoAb 5B3 has at least two distinct idiotopes at its combining site and MoAb MA208 also has two. Four different anti-idiotypic MoAbs (Ab2) could induce anti-anti-idiotypic antibodies (Ab3) specific to their respective immunizing anti-idiotypic MoAbs. Anti-anti-idiotypic MoAb M7-625 antiserum (at least a part of the antibodies) have the same reactivity as MoAb MA208, since the serum competed with the binding of MoAb MA208 against CEA and contained the antibody population reactive with purified CEA in immunoblotting assay. These results suggest that anti-idiotypic MoAb M7-625 bears the internal image of the antigen (CEA) and induces the anti-anti-idiotypic antibodies specific to CEA. Therefore, an anti-idiotypic antibody bearing the internal image of a tumor associated antigen might be used as a possible tool for vaccination or immunotherapy against malignant tumors as an antigen specific immunomodulator.

摘要

抗独特型单克隆抗体(MoAbs)是在同基因系统中针对抗癌胚抗原(CEA)单克隆抗体5B3(IgG1)制备的,该抗体与CEA上的碳水化合物部分发生反应,以及单克隆抗体MA208(IgG1),其与CEA上的肽发生反应。抗独特型单克隆抗体T3 - 503和T4 - 202识别单克隆抗体5B3的独特型;抗独特型单克隆抗体M7 - 049和M7 - 625则针对单克隆抗体MA208识别其独特型。独特型图谱显示,单克隆抗体5B3在其结合位点至少有两个不同的独特位,单克隆抗体MA208也有两个。四种不同的抗独特型单克隆抗体(Ab2)可以诱导针对各自免疫的抗独特型单克隆抗体的抗抗独特型抗体(Ab3)。抗抗独特型单克隆抗体M7 - 625抗血清(至少部分抗体)具有与单克隆抗体MA208相同的反应性,因为该血清与单克隆抗体MA208与CEA的结合发生竞争,并且在免疫印迹分析中含有与纯化的CEA反应的抗体群体。这些结果表明,抗独特型单克隆抗体M7 - 625具有抗原(CEA)的内影像,并诱导针对CEA的抗抗独特型抗体。因此,具有肿瘤相关抗原内影像的抗独特型抗体可能作为一种可能的工具,作为抗原特异性免疫调节剂用于针对恶性肿瘤的疫苗接种或免疫治疗。

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引用本文的文献

1
Preventive DNA vaccination against CEA-expressing tumors with anti-idiotypic scFv6.C4 DNA in CEA-expressing transgenic mice.在表达癌胚抗原(CEA)的转基因小鼠中,用抗独特型单链抗体片段6.C4 DNA进行预防性DNA疫苗接种以对抗表达CEA的肿瘤。
Cancer Immunol Immunother. 2017 Mar;66(3):333-342. doi: 10.1007/s00262-016-1940-4. Epub 2016 Dec 2.
2
Monoclonal antibodies as effective therapeutic agents for solid tumors.单克隆抗体作为实体瘤的有效治疗药物。
Cancer Sci. 2004 Aug;95(8):621-5. doi: 10.1111/j.1349-7006.2004.tb03319.x.
3
Preparation and characterization of anti-anti-idiotypic monoclonal antibody ("Ab1-like Ab3") in relation to carcinoembryonic antigen.
与癌胚抗原相关的抗抗独特型单克隆抗体(“Ab1样Ab3”)的制备与表征
J Clin Lab Anal. 2002;16(6):279-89. doi: 10.1002/jcla.10058.
4
Induction of delayed-type hypersensitivity responses by monoclonal anti-idiotypic antibodies to tumor cells expressing carcinoembryonic antigen and tumor-associated glycoprotein-72.用针对表达癌胚抗原和肿瘤相关糖蛋白-72的肿瘤细胞的单克隆抗独特型抗体诱导迟发型超敏反应。
Cancer Immunol Immunother. 1993 May;36(5):281-92. doi: 10.1007/BF01741166.
5
Immune response to the carcinoembryonic antigen in patients treated with an anti-idiotype antibody vaccine.接受抗独特型抗体疫苗治疗的患者对癌胚抗原的免疫反应。
J Clin Invest. 1995 Jul;96(1):334-42. doi: 10.1172/JCI118039.