ETH Zürich HCI G396, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Wolfgang-Pauli-Strasse 10, CH-8093 Zürich, Switzerland.
Exp Cell Res. 2010 Mar 10;316(5):836-47. doi: 10.1016/j.yexcr.2009.11.004. Epub 2009 Nov 12.
Matrix metalloproteinases (MMPs), a group of more than 20 zinc-containing endopeptidases, are up-regulated in many diseases, but the use of MMP inhibitors for therapeutic purposes has often been disappointing, possibly for the limited specificity of the drugs used in clinical trials. In principle, individual MMPs could be specifically drugged by monoclonal antibodies, either by inhibition of their catalytic activity or by antibody-based pharmacodelivery strategies. In this article we describe the isolation and affinity maturation of recombinant antibodies (SP1, SP2, SP3) specific to the murine catalytic domains of MMP-1A, MMP-2 and MMP-3. These novel reagents allowed a systematic comparative immunofluorescence analysis of the expression patterns of their cognate antigens in a variety of healthy, cancerous and arthritic murine tissues. While all three MMPs were strongly expressed in tumor and arthritis specimens, MMP-1A was completely undetectable in the normal tissues tested, while MMP-2 and MMP-3 exhibited a weak expression in certain normal tissues (e.g., liver). The new antibodies may serve as building blocks for the development of antibody-based therapy strategies in mouse models of pathology.
基质金属蛋白酶（MMPs）是一组含有 20 多种锌的内肽酶，在许多疾病中上调，但 MMP 抑制剂在治疗中的应用常常令人失望，可能是因为临床试验中使用的药物特异性有限。原则上，可以通过单克隆抗体特异性地给单个 MMP 药物治疗，要么抑制其催化活性，要么通过抗体为基础的药物输送策略。在本文中，我们描述了针对 MMP-1A、MMP-2 和 MMP-3 的鼠源催化结构域的特异性重组抗体（SP1、SP2、SP3）的分离和亲和力成熟。这些新型试剂允许对其同源抗原在各种健康、癌症和关节炎鼠组织中的表达模式进行系统的比较免疫荧光分析。虽然所有三种 MMP 在肿瘤和关节炎标本中均强烈表达，但 MMP-1A 在测试的正常组织中完全无法检测到，而 MMP-2 和 MMP-3 在某些正常组织（如肝脏）中表达较弱。新的抗体可以作为在病理学的小鼠模型中开发抗体为基础的治疗策略的构建块。
