Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

Jonathan E. Zuckerman; Ismael Gritli; Anthony TolcherJeremy D. HeidelDean LimRobert MorganBartosz ChmielowskiAntoni RibasMark E. DavisYun Yen

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Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

机译：Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

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Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)-based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase I clinical trial where 24 patients with different cancers were treated with CALAA-01 and compare those results to data obtained from multispecies animal studies to provide a detailed example of translating this class of nanoparticles from animals to humans. The pharmacokinetics of CALAA-01 in mice, rats, monkeys, and humans show fast elimination and reveal that the maximum concentration obtained in the blood after i.v. administration correlates with body weight across all species. The safety profile of CALAA-01 in animals is similarly obtained in humans except that animal kidney toxicities are not observed in humans; this could be due to the use of a predosing hydration protocol used in the clinic. Taken in total, the animal models do appear to predict the behavior of CALAA-01 in humans.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第31期|11449-11454|共6页
作者
Jonathan E. Zuckerman; Ismael Gritli; Anthony TolcherJeremy D. HeidelDean LimRobert MorganBartosz ChmielowskiAntoni RibasMark E. DavisYun Yen;
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作者单位

Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;

College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan;

South Texas Accelerated Research Therapeutics, San Antonio, TX 78229Informulate, Madison, WI 53704Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010Department of Medicine, Division of Hematology Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
translational medicine; DNA proliferation; DNA replication; maximum tolerance dose; dose limiting toxicity;

Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

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