Passive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies.
Passive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies.
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DOI：
10.1371/journal.pone.0135774
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Davies P
中科院分区：
文献类型：
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作者：
d'Abramo C;Acker CM;Jimenez H;Davies P
我们实验室和其他一些实验室最近的工作强烈表明，免疫疗法可能是预防携带人P301 L突变的JNPL 3转基因小鼠中tau积累的有效手段。本研究的目的是测试多种特异性tau单克隆抗体在JNPL 3中的功效。从3月龄开始，用每周腹膜内注射盐水或纯化的tau单克隆抗体（10 mg/Kg）处理小鼠4个月，所述纯化的tau单克隆抗体对病理性tau具有不同的特异性：CP 13（pSer 202）、RZ 3（pThr 231）和PG 5（pSer 409）。正如预期的那样，并非所有测试的抗体在所述剂量下都显示出预防tau病理学发展的功效，其中一些甚至使病理学情况恶化。仅通过用CP 13靶向pSer 202表位，获得了皮质和后脑中不溶性或可溶性tau的显著减少。在这里，我们报告了在体内筛选多种tau抗体的重要性，以选择抗体指导未来的临床研究。
Recent work from our lab and few others have strongly suggested that immunotherapy could be an effective means of preventing the development of tau accumulation in JNPL3 transgenic mice, carrying the human P301L mutation. The aim of this study was to test the efficacy of a variety of specific tau monoclonal antibodies in JNPL3. Starting at 3 months of age, mice were treated for 4 months with weekly intraperitoneal injections of saline or purified tau monoclonal antibodies (10mg/Kg) different in specificity for pathological tau: CP13 (pSer202), RZ3 (pThr231) and PG5 (pSer409). As expected, not all the antibodies tested showed efficacy at preventing the development of tau pathology at the described dose, with some of them even worsening the pathological scenario. Only by targeting the pSer202 epitope with CP13 was a conspicuous reduction of insoluble or soluble tau in cortex and hindbrain obtained. Here we report about the importance of screening in vivo multiple tau antibodies in order to select the antibodies to direct into future clinical studies.