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مواد زیستی
جزئیات رویداد
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  • synapse-directed delivery of immunomodulators using t-cell-conjugated nanoparticles

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    جزئیات بیشتر مقاله
    • تاریخ ارائه: 1391/01/01
    • تاریخ انتشار در تی پی بین: 1391/01/01
    • تعداد بازدید: 726
    • تعداد پرسش و پاسخ ها: 0
    • شماره تماس دبیرخانه رویداد: -
     regulating molecular interactions in the t-cell synapse to prevent autoimmunity or, conversely, to boost anti-tumor immunity has long been a goal in immunotherapy. however, delivering therapeutically meaningful doses of immune-modulating compounds into the synapse represents a major challenge. here, we report that covalent coupling of maleimide-functionlized nanoparticles (nps) to free thiol groups on t-cell membrane proteins enables efficient delivery of compounds into the t-cell synapse. we demonstrate that surface-linked nps are rapidly polarized toward the nascent immunological synapse (is) at the t-cell/apc contact zone during antigen recognition. to translate these findings into a therapeutic application we tested the np delivery of nsc-87877, a dual inhibitor of shp1 and shp2, key phosphatases that downregulate t-cell receptor activation in the synapse, in the context of adoptive t cell therapy of cancer. conjugating nsc-87877-loaded nps to the surface of tumor-specific t cells just prior to adoptive transfer into mice with advanced prostate cancer promoted a much greater t-cell expansion at the tumor site, relative to co-infusing the same drug dose systemically, leading to enhanced survival of treated animals. in summary, our studies support the application of t-cell-linked synthetic nps as efficient drug delivery vehicles into the is, as well as the broad applicability of this new paradigm for therapeutically modulating signaling events at the t-cell/apc interface.

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