Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells. (February 2017)

• Record Type: Journal Article
• Authors: Jones, R. Brad; Mueller, Stephanie; Kumari, Sudha; Vrbanac, Vlad; Genel, Shy; Tager, Andrew M.; Allen, Todd M.; Walker, Bruce D.; Irvine, Darrell J.
• Is Part Of: Biomaterials. Volume 117(2017)
• Page Start: 44
• Page End: 53
• Publication Date: 2017-02
• Subjects: Drug delivery -- Cytotoxic T lymphocytes -- Lipid nanocapsules -- Immunotherapy -- T-pharmacyte; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2016.11.048
• Languages: English
• ISSNs: 0142-9612

Abstract

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 .