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高剂量、未标记、非特异性抗体预处理:对人黑色素瘤异种移植瘤中特异性抗体定位的影响。

High-dose, unlabeled, nonspecific antibody pretreatment: influence on specific antibody localization to human melanoma xenografts.

作者信息

Wahl R L, Wilson B S, Liebert M, Beierwaltes W H

出版信息

Cancer Immunol Immunother. 1987;24(3):221-4. doi: 10.1007/BF00205633.

DOI:10.1007/BF00205633
PMID:3594484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11037974/
Abstract

Nonspecific uptake of radiolabeled monoclonal antibodies in normal tissues is a significant problem for tumor imaging. A potential means of decreasing nonspecific antibody binding is to "blockade" nonspecific antibody binding sites by predosing with cold, nonspecific isotype-matched antibody, before injecting specific antibody. Nontumor-specific murine monoclonal antibody LK2H10 (IgG1) or Ab-1 (IgG2a) was given i.v. at doses of 0 to 3.5 mg to nude mice with xenografts of human melanoma. These mice were then given i.v. 4 micrograms of 131I anti-high molecular weight antigen of melanoma (HMWMAA) monoclonal antibody 763.24T (IgG1) or 225.28S (IgG2a), respectively. These mice were also given a tracer dose of 125I LK2H10 or Ab-1, respectively. Specific tumor uptake of anti-HMWMAA antibodies was see in all cases. No drop in tumor or nontumor uptake was demonstrated for either of the tumor-specific or nonspecific monoclonal antibodies due to nonspecific monoclonal antibody pretreatment. These data suggest that high doses of isotype-matched unlabeled nonspecific monoclonal antibody given before 131I tumor-specific monoclonal antibody, will not enhance tumor imaging.

摘要

放射性标记单克隆抗体在正常组织中的非特异性摄取是肿瘤成像中的一个重要问题。减少非特异性抗体结合的一种潜在方法是在注射特异性抗体之前,预先给予冷的、非特异性的同型匹配抗体,以“阻断”非特异性抗体结合位点。将非肿瘤特异性鼠单克隆抗体LK2H10(IgG1)或Ab-1(IgG2a)以0至3.5毫克的剂量静脉注射给有人黑色素瘤异种移植的裸鼠。然后分别给这些小鼠静脉注射4微克的131I抗黑色素瘤高分子量抗原(HMWMAA)单克隆抗体763.24T(IgG1)或225.28S(IgG2a)。这些小鼠还分别给予了示踪剂量的125I LK2H10或Ab-1。在所有情况下均可见抗HMWMAA抗体的特异性肿瘤摄取。由于非特异性单克隆抗体预处理,肿瘤特异性或非特异性单克隆抗体的肿瘤或非肿瘤摄取均未降低。这些数据表明,在131I肿瘤特异性单克隆抗体之前给予高剂量的同型匹配未标记非特异性单克隆抗体,不会增强肿瘤成像。

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本文引用的文献

1
Distribution and molecular characterization of a cell-surface and a cytoplasmic antigen detectable in human melanoma cells with monoclonal antibodies.利用单克隆抗体在人黑色素瘤细胞中检测到的一种细胞表面抗原和一种细胞质抗原的分布及分子特征
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Imaging of human melanoma xenografts in nude mice with a radiolabeled monoclonal antibody.用放射性标记的单克隆抗体对裸鼠体内的人黑色素瘤异种移植瘤进行成像。
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Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody.通过单克隆抗体对无胸腺小鼠体内人乳腺肿瘤进行放射性定位。
Cancer Res. 1983 Feb;43(2):736-42.
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Monoclonal antibody radioimmunodetection of human-derived colon cancer.人源结肠癌的单克隆抗体放射免疫检测
Invest Radiol. 1983 Jan-Feb;18(1):58-62. doi: 10.1097/00004424-198301000-00010.
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Level of a membrane-bound high-molecular-weight melanoma-associated antigen and a cytoplasmic melanoma-associated antigen in surgically removed tissues and in sera from patients with melanoma.手术切除组织及黑色素瘤患者血清中膜结合型高分子量黑色素瘤相关抗原和细胞质黑色素瘤相关抗原的水平。
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