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

Simple item page
dc.citation.firstpage67
dc.citation.journalTitleBiomaterials
dc.citation.lastpage75
dc.citation.volumeNumber163
dc.contributor.authorLeach, David G.
dc.contributor.authorDharmaraj, Neeraja
dc.contributor.authorPiotrowski, Stacey L.
dc.contributor.authorLopez-Silva, Tania L.
dc.contributor.authorLei, Yu L.
dc.contributor.authorSikora, Andrew G.
dc.contributor.authorYoung, Simon
dc.contributor.authorHartgerink, Jeffrey D.
dc.date.accessioned2019-12-11T15:44:28Z
dc.date.available2019-12-11T15:44:28Z
dc.date.issued2018
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.
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.
dc.identifier.digitalnihms943399
dc.identifier.doihttps://doi.org/10.1016/j.biomaterials.2018.01.035
dc.identifier.urihttps://hdl.handle.net/1911/107862
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.subject.keywordSTINGel
dc.subject.keywordImmunotherapy
dc.subject.keywordExtended drug release
dc.subject.keywordPeptide hydrogel
dc.subject.keywordIntratumoral injection
dc.titleSTINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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