Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Zuckerman JE,Gritli I,Tolcher A,Heidel JD,Lim D,Morgan R,Chmielowski B,Ribas A,Davis ME,Yen Ydoi
10.1073/pnas.1411393111subject
Has Abstractpub_date
2014-08-05 00:00:00pages
11449-54issue
31eissn
0027-8424issn
1091-6490pii
1411393111journal_volume
111pub_type
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