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用单克隆抗体靶向癌症微转移灶:结合位点障碍

Targeting cancer micrometastases with monoclonal antibodies: a binding-site barrier.

作者信息

Saga T, Neumann R D, Heya T, Sato J, Kinuya S, Le N, Paik C H, Weinstein J N

机构信息

Nuclear Medicine Department, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8999-9003. doi: 10.1073/pnas.92.19.8999.

Abstract

Monoclonal antibodies penetrate bulky tumors poorly after intravenous administration, in part because of specific binding to the target antigen. Experiments presented here demonstrate an analogous phenomenon in micrometastases; poor antibody penetration, attributable to a "binding-site barrier" phenomenon, can be seen in guinea pig micrometastases as small as 300 microns in diameter. Increasing the dose of antibody can partially overcome this limitation, but at a cost in specificity.

摘要

静脉注射后,单克隆抗体在实体瘤中的渗透效果不佳,部分原因是其与靶抗原的特异性结合。本文展示的实验在微转移灶中证实了类似现象;在直径小至300微米的豚鼠微转移灶中,可观察到因“结合位点屏障”现象导致的抗体渗透不良。增加抗体剂量可部分克服这一限制,但会牺牲特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee7b/41095/3fe13132fd15/pnas01497-0477-a.jpg

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