Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells
Author(s)Mueller, Stephanie; Vrbanac, Vlad; Genel, Shy; Tager, Andrew M.; Allen, Todd M.; Jones, Richard Bradley; Kumari, Sudha; Walker, Bruce; Irvine, Darrell J; ... Show more Show less
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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.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering
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.
Author's final manuscript