Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells

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• 作者：R. Brad Jones^a ; ^b ; ^c ; Stephanie Mueller^a ; ^c ; Sudha Kumari^a ; ^c ; Vlad Vrbanac^a ; ^d ; Shy Genel^e ; Andrew M. Tager^a ; Todd M. Allen^a ; Bruce D. Walker^a ; ^f ; ^g ; ^h ; Darrell J. Irvine^a ; ^c ; ^g ; ^h ; ⁱ ; ^{djirvine@mit.edu}
• 关键词：Drug delivery ; Cytotoxic T lymphocytes ; Lipid nanocapsules ; Immunotherapy ; T-pharmacyte
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：117
• 期：Complete
• 页码：44-53
• 全文大小：3296 K
• 卷排序：117

文摘

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.