Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species.

TitleImaging-assisted nanoimmunotherapy for atherosclerosis in multiple species.
Publication TypeJournal Article
Year of Publication2019
AuthorsBinderup T, Duivenvoorden R, Fay F, van Leent MMT, Malkus J, Baxter S, Ishino S, Zhao Y, Sanchez-Gaytan B, Teunissen AJP, Frederico YCA, Tang J, Carlucci G, Lyashchenko S, Calcagno C, Karakatsanis N, Soultanidis G, Senders ML, Robson PM, Mani V, Ramachandran S, Lobatto ME, Hutten BA, Granada JF, Reiner T, Swirski FK, Nahrendorf M, Kjaer A, Fisher EA, Fayad ZA, PĂ©rez-Medina C, Mulder WJM
JournalSci Transl Med
Volume11
Issue506
Date Published2019 08 21
ISSN1946-6242
KeywordsAnimals, Apolipoproteins E, Atherosclerosis, Disease Models, Animal, Female, Imaging, Three-Dimensional, Immunotherapy, Lipoproteins, HDL, Magnetic Resonance Imaging, Male, Mice, Inbred C57BL, Nanomedicine, Positron-Emission Tomography, Rabbits, Simvastatin, Species Specificity, Swine, Tissue Distribution
Abstract

Nanomedicine research produces hundreds of studies every year, yet very few formulations have been approved for clinical use. This is due in part to a reliance on murine studies, which have limited value in accurately predicting translational efficacy in larger animal models and humans. Here, we report the scale-up of a nanoimmunotherapy from mouse to large rabbit and porcine atherosclerosis models, with an emphasis on the solutions we implemented to overcome production and evaluation challenges. Specifically, we integrated translational imaging readouts within our workflow to both analyze the nanoimmunotherapeutic's in vivo behavior and assess treatment response in larger animals. We observed our nanoimmunotherapeutic's anti-inflammatory efficacy in mice, as well as rabbits and pigs. Nanoimmunotherapy-mediated reduction of inflammation in the large animal models halted plaque progression, supporting the approach's translatability and potential to acutely treat atherosclerosis.

DOI10.1126/scitranslmed.aaw7736
Alternate JournalSci Transl Med
PubMed ID31434756
PubMed Central IDPMC7328283
Grant ListR01 HL125703 / HL / NHLBI NIH HHS / United States
R01 HL144072 / HL / NHLBI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 EB009638 / EB / NIBIB NIH HHS / United States
R01 HL118440 / HL / NHLBI NIH HHS / United States
R01 HL071021 / HL / NHLBI NIH HHS / United States
P01 HL131478 / HL / NHLBI NIH HHS / United States

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065