STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy

Simple item page
dc.citation.firstpage67en_US
dc.citation.journalTitleBiomaterialsen_US
dc.citation.lastpage75en_US
dc.citation.volumeNumber163en_US
dc.contributor.authorLeach, David G.en_US
dc.contributor.authorDharmaraj, Neerajaen_US
dc.contributor.authorPiotrowski, Stacey L.en_US
dc.contributor.authorLopez-Silva, Tania L.en_US
dc.contributor.authorLei, Yu L.en_US
dc.contributor.authorSikora, Andrew G.en_US
dc.contributor.authorYoung, Simonen_US
dc.contributor.authorHartgerink, Jeffrey D.en_US
dc.date.accessioned2019-12-11T15:44:28Zen_US
dc.date.available2019-12-11T15:44:28Zen_US
dc.date.issued2018en_US
dc.description.abstractRecent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call “STINGel.” STINGel is an injectable peptide hydrogel that localizes and provides controlled release of CDN delivery, showing an 8-fold slower release rate compared to a standard collagen hydrogel. The carrier hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles to form a nanofibrous matrix and is easily delivered by syringe. The highly localized delivery of CDN from this nanostructured biomaterial affects the local histological response in a subcutaneous model, and dramatically improves overall survival in a challenging murine model of head and neck cancer compared to CDN alone or CDN delivered from a collagen hydrogel. This study demonstrates the feasibility of biomaterial-based immunotherapy platforms like STINGel as strategies for increasing the efficacy of CDN immunotherapies.en_US
dc.identifier.citationLeach, David G., Dharmaraj, Neeraja, Piotrowski, Stacey L., et al.. "STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy." <i>Biomaterials,</i> 163, (2018) Elsevier: 67-75. https://doi.org/10.1016/j.biomaterials.2018.01.035.en_US
dc.identifier.digitalnihms943399en_US
dc.identifier.doihttps://doi.org/10.1016/j.biomaterials.2018.01.035en_US
dc.identifier.urihttps://hdl.handle.net/1911/107862en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordSTINGelen_US
dc.subject.keywordImmunotherapyen_US
dc.subject.keywordExtended drug releaseen_US
dc.subject.keywordPeptide hydrogelen_US
dc.subject.keywordIntratumoral injectionen_US
dc.titleSTINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapyen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
nihms943399.pdf
Size:
1.1 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Bioengineering Publications
Chemistry Publications