An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity

Mark Baer; Teiji Sawa; Peter Flynn; Kenneth Luehrsen; David Martinez; Jeanine P. Wiener-Kronish; Geoffrey Yarranton; Christopher Bebbington

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An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity

机译：铜绿假单胞菌PcrV抗原特异的工程化的人类抗体Fab片段具有强大的抗菌活性

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Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute lung injury and mortality through the delivery of exotoxins by the type III secretion system (TTSS). PcrV is an important structural protein of the TTSS. An engineered human antibody Fab fragment that binds to the P. aeruginosa PcrV protein with high affinity has been identified and has potent in vitro neutralization activity against the TTSS. The instillation of a single dose of Fab into the lungs of mice provided protection against lethal pulmonary challenge of P. aeruginosa and led to a substantial reduction of viable bacterial counts in the lungs. These results demonstrate that blocking of the TTSS by a Fab lacking antibody Fc-mediated effector functions can be sufficient for the effective clearance of pulmonary P. aeruginosa infection.

机译：铜绿假单胞菌是一种机会性病原体，通过III型分泌系统（TTSS）释放外毒素可导致急性肺损伤和致死。 PcrV是TTSS的重要结构蛋白。与 P结合的工程化的人抗体Fab片段。铜绿假单胞菌PcrV蛋白具有高亲和力，并且对TTSS具有强大的体外中和活性。将单剂量的Fab滴入小鼠的肺部可提供保护作用，以防止致命的肺部Pem攻击。铜绿假单胞菌，导致肺中活菌数量大幅减少。这些结果证明，通过缺乏抗体Fc介导的效应子功能的Fab对TTSS的阻断可以足以有效清除肺 P。铜绿菌感染。 展开▼

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《Infection and immunity》 |2009年第3期|共8页

作者
Mark Baer; Teiji Sawa; Peter Flynn; Kenneth Luehrsen; David Martinez; Jeanine P. Wiener-Kronish; Geoffrey Yarranton; Christopher Bebbington;
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中图分类医学免疫学;

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专利

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机译：人-人杂交瘤分泌具有高效中和活性的抗铜绿假单胞菌外毒素-A单克隆抗体

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机译：用针对VEGF受体2的完整人抗体Fab片段有效中和VEGF的生物学活性

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机译：通过使用编码癌胚抗原特异性的单链片段化抗体的完整人类基因来增强抗肿瘤活性

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机译：人合成，半合成和Na ve've免疫文库，用于有效地分离抗原特异性抗体的分离分离抗原特异性抗体

5. A novel approach to control and regulate the classical complement pathway: Highly specific inhibition of C1q globular head binding to human IgG using an engineered single chain antibody variable fragment; recruiting C1q to HER2 /neu positive cells using truncated bispecific antibodies [D] . Hwang, Hee Young 2007

机译：一种控制和调节经典补体途径的新方法：使用工程化的单链抗体可变片段高度特异性地抑制C1q球头与人IgG的结合；使用截短的双特异性抗体将C1q募集到HER2 / neu阳性细胞

6. An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity [O] . Mark Baer, Teiji Sawa, Peter Flynn, 2009

机译：铜绿假单胞菌PcrV抗原特异的工程化的人类抗体Fab片段具有强大的抗菌活性

7. An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity▿ [O] . Baer, Mark, Sawa, Teiji, Flynn, Peter, 2008

机译：铜绿假单胞菌PcrV抗原特异的工程化人类抗体Fab片段具有强大的抗菌活性▿

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1. 具有融合至常规Fab片段的单域抗原结合片段的二价抗体 [P] . 中国专利： CN106188305A . 2016-12-07

2. 针对铜绿假单胞菌PCRV抗原的抗体 [P] . 中国专利： CN101910197B . 2014.09.24

3. antibody, antibody antigen binding fragment, pharmaceutical composition, methods for treating and / or prophylaxis of pseudomona infection and for producing an antibody, pseudomona infection diagnostic agent, pseudomonas aeruginosa detection kit, polynucleotide, vector, and , transformed host cell [P] . 外国专利： BR112016006428A2 . 2017-09-26

机译：抗体，抗体抗原结合片段，药物组合物，治疗和/或预防假单胞菌感染和产生抗体的方法，假单胞菌感染诊断剂，铜绿假单胞菌检测试剂盒，多核苷酸，载体和转化宿主细胞

4. antibody or antigen-binding fragment of the antibody, polynucleotide, vector, cell, artificial immunocyte, methods for producing an antibody or an antigen-binding fragment of the antibody, to produce a molecule that binds to human cd3 and cd3 of cynomolgus monkey and human gprc5d, medicinal composition for treatment and / or prevention, molecules having antigen binding activity and that bind to human cd3 and cynomolgus monkey cd3 and human gprc5d, and uses to prepare a drug to treat and / or prevent a cancer, to induce cytotoxicity to cells expressing gprc5d and to redirect t cells to cells expressing gprc5d [P] . 外国专利： BR112019016204A2 . 2020-07-07

机译：抗体或抗体的抗原结合片段，多核苷酸，载体，细胞，人工免疫细胞，产生抗体或抗体的抗原结合片段的方法，以产生与食蟹猴和人的人cd3和cd3结合的分子gprc5d，用于治疗和/或预防的药物组合物，具有抗原结合活性并与人cd3和食蟹猴cd3和人gprc5d结合的分子，并用于制备治疗和/或预防癌症，诱导对细胞产生细胞毒性的药物表达gprc5d并将t细胞重定向到表达gprc5d的细胞

5. antibodies to pseudomonas aeruginosa pcrv antigen [P] . 外国专利： BRPI0819598A2 . 2017-05-09

机译：铜绿假单胞菌pcrv抗原抗体

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An Engineered Human Antibody Fab Fragment Specific for Pseudomonas aeruginosa PcrV Antigen Has Potent Antibacterial Activity

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