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Engulfing tumors with synthetic extracellular matrices for cancer

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dc.contributor.author Hori, Yuki
dc.contributor.author Stern, Patrick
dc.contributor.author Hynes, Richard O.
dc.contributor.author Irvine, Darrell J.
dc.date.accessioned 2012-10-05T18:47:29Z
dc.date.available 2012-10-05T18:47:29Z
dc.date.issued 2009-12
dc.identifier.issn 0142-9612
dc.identifier.issn 1878-5905
dc.identifier.uri http://hdl.handle.net/1721.1/73661
dc.description available in PMC 2010 June 1. en_US
dc.description.abstract Local immunotherapies are under investigation for the treatment of unresectable tumors and sites of solid tumor resection to prevent local recurrence. Successful local therapy could also theoretically elicit systemic immune responses against cancer. Here we explored the delivery of therapeutic dendritic cells (DCs), cytokines, or other immunostimulatory factors to tumors via the use of ‘self-gelling’ hydrogels based on the polysaccharide alginate, injected peritumorally around established melanoma lesions. Peritumoral injection of alginate matrices loaded with DCs and/or an interleukin-15 superagonist (IL-15SA) around 14-day established ova-expressing B16F0 murine melanoma tumors promoted immune cell accumulation in the peritumoral matrix, and matrix infiltration correlated with tumor infiltration by leukocytes. Single injections of IL-15SA-carrying gels concentrated the cytokine in the tumor site ∼40-fold compared to systemic injection and enabled a majority of treated animals to suppress tumor growth for a week or more. Further, we found that single injections of alginate matrices loaded with IL-15SA and the Toll-like receptor ligand CpG or two injections of gels carrying IL-15SA alone could elicit comparable anti-tumor activity without the need for exogenous DCs. Thus, injectable alginate gels offer an attractive platform for local tumor immunotherapy, and facilitate combinatorial treatments designed to promote immune responses locally at a tumor site while limiting systemic exposure to potent immunomodulatory factors. en_US
dc.description.sponsorship United States. Defense Advanced Research Projects Agency ( (contract # W81XWH-04-C-0139) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (NIH Grant EB007280) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (NIH Grant U54-CA126515) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (NIH Grant U54-CA112967) en_US
dc.description.sponsorship National Science Foundation (U.S.) (award 0348259 ) en_US
dc.language.iso en_US
dc.publisher Elsevier B.V. en_US
dc.relation.isversionof http://dx.doi.org/10.1016/j.biomaterials.2009.08.037 en_US
dc.rights Creative Commons Attribution-Noncommercial-Share Alike 3.0 en_US
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/ en_US
dc.source PMC en_US
dc.title Engulfing tumors with synthetic extracellular matrices for cancer en_US
dc.type Article en_US
dc.identifier.citation Hori, Yuki et al. “Engulfing Tumors with Synthetic Extracellular Matrices for Cancer Immunotherapy.” Biomaterials 30.35 (2009): 6757–6767. Web. en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Materials Science and Engineering en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biological Engineering en_US
dc.contributor.department David H. Koch Institute for Integrative Cancer Research at MIT en_US
dc.contributor.mitauthor Hori, Yuki
dc.contributor.mitauthor Stern, Patrick
dc.contributor.mitauthor Hynes, Richard O.
dc.contributor.mitauthor Irvine, Darrell J.
dc.relation.journal Biomaterials en_US
dc.identifier.mitlicense OPEN_ACCESS_POLICY en_US
dc.eprint.version Author's final manuscript en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Hori, Yuki; Stern, Patrick J.; Hynes, Richard O.; Irvine, Darrell J. en


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