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dc.contributor.authorZhang, Yuan
dc.contributor.authorLi, Na
dc.contributor.authorSuh, Heikyung
dc.contributor.authorIrvine, Darrell J
dc.date.accessioned2018-05-02T18:13:15Z
dc.date.available2018-05-02T18:13:15Z
dc.date.issued2018-01
dc.date.submitted2017-04
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/1721.1/115183
dc.description.abstractImmunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)-2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes, cytokine production, and granzyme expression, demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus, surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities.en_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/S41467-017-02251-3en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNature Communicationsen_US
dc.titleNanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicityen_US
dc.typeArticleen_US
dc.identifier.citationZhang, Yuan et al. “Nanoparticle Anchoring Targets Immune Agonists to Tumors Enabling Anti-Cancer Immunity Without Systemic Toxicity.” Nature Communications 9, 1 (January 2018) © 2018 The Author(s)en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Materials Science and Engineeringen_US
dc.contributor.mitauthorZhang, Yuan
dc.contributor.mitauthorLi, Na
dc.contributor.mitauthorSuh, Heikyung
dc.contributor.mitauthorIrvine, Darrell J
dc.relation.journalNature Communicationsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-04-27T14:41:26Z
dspace.orderedauthorsZhang, Yuan; Li, Na; Suh, Heikyung; Irvine, Darrell J.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-2931-7592
dc.identifier.orcidhttps://orcid.org/0000-0003-0787-298X
mit.licensePUBLISHER_CCen_US


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