Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells
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 cel...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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Elsevier BV
2018
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| Online Access: | http://hdl.handle.net/1721.1/117770 https://orcid.org/0000-0003-4083-335X https://orcid.org/0000-0003-2705-7245 https://orcid.org/0000-0001-6122-9245 |
| _version_ | 1811076821210365952 |
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| author | Mueller, Stephanie Vrbanac, Vlad Genel, Shy Tager, Andrew M. Allen, Todd M. Jones, Richard Bradley Kumari, Sudha Walker, Bruce Irvine, Darrell J |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Mueller, Stephanie Vrbanac, Vlad Genel, Shy Tager, Andrew M. Allen, Todd M. Jones, Richard Bradley Kumari, Sudha Walker, Bruce Irvine, Darrell J |
| author_sort | Mueller, Stephanie |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:28:06Z |
| format | Article |
| id | mit-1721.1/117770 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:28:06Z |
| publishDate | 2018 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1177702022-09-30T21:22:13Z Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells Mueller, Stephanie Vrbanac, Vlad Genel, Shy Tager, Andrew M. Allen, Todd M. Jones, Richard Bradley Kumari, Sudha Walker, Bruce Irvine, Darrell J Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Koch Institute for Integrative Cancer Research at MIT Jones, Richard Bradley Kumari, Sudha Walker, Bruce Irvine, Darrell J 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. Ragon Institute of MGH, MIT and Harvard National Institutes of Health (U.S.) (IH (AI111860) 2018-09-17T12:42:03Z 2018-09-17T12:42:03Z 2017-02 2018-09-06T18:33:06Z Article http://purl.org/eprint/type/JournalArticle 01429612 http://hdl.handle.net/1721.1/117770 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. https://orcid.org/0000-0003-4083-335X https://orcid.org/0000-0003-2705-7245 https://orcid.org/0000-0001-6122-9245 http://dx.doi.org/10.1016/J.BIOMATERIALS.2016.11.048 Biomaterials Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Mueller, Stephanie Vrbanac, Vlad Genel, Shy Tager, Andrew M. Allen, Todd M. Jones, Richard Bradley Kumari, Sudha Walker, Bruce Irvine, Darrell J Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells |
| title | Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells |
| title_full | Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells |
| title_fullStr | Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells |
| title_full_unstemmed | Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells |
| title_short | Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells |
| title_sort | antigen recognition triggered drug delivery mediated by nanocapsule functionalized cytotoxic t cells |
| url | http://hdl.handle.net/1721.1/117770 https://orcid.org/0000-0003-4083-335X https://orcid.org/0000-0003-2705-7245 https://orcid.org/0000-0001-6122-9245 |
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