|Title||Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||R. Jones, B, Mueller, S, Kumari, S, Vrbanac, V, Genel, S, Tager, AM, Allen, TM, Walker, BD, Irvine, DJ|
|Pagination||44 - 53|
|Keywords||Cytotoxic T lymphocytes, Drug delivery, hiv-1 replication, Immunotherapy, Lipid nanocapsules, lymph-node, lymphocytes, mechanisms, nanomaterials, Nanoparticles, perforin, responses, stimulation, T-pharmacyte, therapies|
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. (C) 2016 Elsevier Ltd. All rights reserved.