dc.contributor.author | Mueller, Stephanie | |
dc.contributor.author | Vrbanac, Vlad | |
dc.contributor.author | Genel, Shy | |
dc.contributor.author | Tager, Andrew M. | |
dc.contributor.author | Allen, Todd M. | |
dc.contributor.author | Jones, Richard Bradley | |
dc.contributor.author | Kumari, Sudha | |
dc.contributor.author | Walker, Bruce | |
dc.contributor.author | Irvine, Darrell J | |
dc.date.accessioned | 2018-09-17T12:42:03Z | |
dc.date.available | 2018-09-17T12:42:03Z | |
dc.date.issued | 2017-02 | |
dc.identifier.issn | 01429612 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/117770 | |
dc.description.abstract | Cytotoxic T-Lymphocytes (CTLs) kill pathogen-infected or transformed cells following interaction of their T-cell receptors (TCRs) with foreign (e.g. virus-derived) peptides bound to MHC-I molecules on the target cell. TCR binding triggers CTLs to secrete perforin, which forms pores in the target cell membrane, promoting target death. Here, we show that by conjugating drug-loaded lipid nanoparticles to the surface of CTLs, their lytic machinery can be co-opted to lyse the cell-bound drug carrier, providing triggered release of drug cargo upon target cell recognition. Protein encapsulated in T-cell-bound nanoparticles was released following culture of CTLs with target cells in an antigen dose- and perforin-dependent manner and coincided with target cell lysis. Using this approach, we demonstrate the capacity of HIV-specific CTLs to deliver an immunotherapeutic agent to an anatomical site of viral replication. This strategy provides a novel means to couple drug delivery to the action of therapeutic cells in vivo. | en_US |
dc.description.sponsorship | Ragon Institute of MGH, MIT and Harvard | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (IH (AI111860) | en_US |
dc.publisher | Elsevier BV | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/J.BIOMATERIALS.2016.11.048 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Jones, R. Brad, Stephanie Mueller, Sudha Kumari, Vlad Vrbanac, Shy Genel, Andrew M. Tager, Todd M. Allen, Bruce D. Walker, and Darrell J. Irvine. “Antigen Recognition-Triggered Drug Delivery Mediated by Nanocapsule-Functionalized Cytotoxic T-Cells.” Biomaterials 117 (February 2017): 44–53. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Institute for Medical Engineering & Science | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Materials Science and Engineering | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Jones, Richard Bradley | |
dc.contributor.mitauthor | Kumari, Sudha | |
dc.contributor.mitauthor | Walker, Bruce | |
dc.contributor.mitauthor | Irvine, Darrell J | |
dc.relation.journal | Biomaterials | 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 |
dc.date.updated | 2018-09-06T18:33:06Z | |
dspace.orderedauthors | Jones, R. Brad; Mueller, Stephanie; Kumari, Sudha; Vrbanac, Vlad; Genel, Shy; Tager, Andrew M.; Allen, Todd M.; Walker, Bruce D.; Irvine, Darrell J. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-4083-335X | |
dc.identifier.orcid | https://orcid.org/0000-0003-2705-7245 | |
dc.identifier.orcid | https://orcid.org/0000-0001-6122-9245 | |
mit.license | PUBLISHER_CC | en_US |