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    In Vivo Expansion of Melanoma-Specific T Cells Using Microneedle Arrays Coated with Immune-Polyelectrolyte Multilayers

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    Author
    Zeng, Q.
    Gammon, J.M.
    Tostanoski, L.H.
    Date
    2017
    Journal
    ACS Biomaterials Science and Engineering
    Publisher
    American Chemical Society
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1021/acsbiomaterials.6b00414
    Abstract
    Microneedles (MNs) are micron-scale polymeric or metallic structures that offer distinct advantages for vaccines by efficiently targeting skin-resident immune cells, eliminating injection-associated pain, and improving patient compliance. These advantages, along with recent studies showing therapeutic benefits achieved using traditional intradermal injections in human cancer patients, suggest MN delivery might enhance cancer vaccines and immunotherapies. We recently developed a new class of polyelectrolyte multilayers based on the self-assembly of model peptide antigens and molecular toll-like receptor agonists (TLRa) into ultrathin, conformal coatings. Here, we reasoned that these immune polyelectrolyte multilayers (iPEMs) might be a useful platform for assembling cancer vaccine components on MN arrays for intradermal delivery from these substrates. Using conserved human melanoma antigens and a potent TLRa vaccine adjuvant, CpG, we show that iPEMs can be assembled on MNs in an automated fashion. These films, prepared with up to 128 layers, are approximately 200 nm thick but provide cancer vaccine cargo loading >225 ?g/cm2. In cell culture, iPEM cargo released from MNs is internalized by primary dendritic cells, promotes activation of these cells, and expands T cells during coculture. In mice, application of iPEM-coated MNs results in the codelivery of tumor antigen and CpG through the skin, expanding tumor-specific T cells during initial MN applications and resulting in larger memory recall responses during a subsequent booster MN application. This study support MNs coated with PEMs built from tumor vaccine components as a well-defined, modular system for generating tumor-specific immune responses, enabling new approaches that can be explored in combination with checkpoint blockade or other combination cancer therapies.
    Sponsors
    This work was supported in part by NSF CAREER Award # 1351688 and the University of Maryland Division of Research (Tier 1). J.M.G. is a grantee of the Pediatric Oncology Student Training award from Alex?s Lemonade Stand Foundation. Y.C.C. is a trainee on NIH Grant # T32 CA154274. L.H.T. is a fellow supported by the NSF Graduate Research Fellowship Program Grant # DGE1322106. C.M.J. is a Damon Runyon- Rachleff Innovator supported by the Damon Runyon Foundation (# DRR3415), and a Young Investigator of the Alliance for Cancer Gene Therapy (# 15051543) and the Melanoma Research Alliance (# 348963).
    Keyword
    cancer
    immunology
    microneedle
    polyelectrolyte multilayer
    self-assembly
    vaccine
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85012247145&doi=10.1021%2facsbiomaterials.6b00414&partnerID=40&md5=66e731a88989b481024bf8c6ad342d9d; http://hdl.handle.net/10713/11350
    ae974a485f413a2113503eed53cd6c53
    10.1021/acsbiomaterials.6b00414
    Scopus Count
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    UMB Open Access Articles 2017

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