TY - JOUR
T1 - A nanoscopic multivalent antigen-presenting carrier for sensitive detection and drug delivery to T Cells
AU - Fahmy, Tarek M.
AU - Schneck, Jonathan P.
AU - Saltzman, W. Mark
N1 - Funding Information:
The authors thank Dr. Alfred Bothwell, Dr. Fadi Lakkis, and Dr. Joe Craft for helpful discussions. They also thank Dr. Kraig Haverstick for early advice on PEG-PAMAM construction. This work was supported by grants from the National Institutes of Health (EB00487 and CA52857) and a career award to TMF from the Wallace Coulter Foundation.
PY - 2007/3
Y1 - 2007/3
N2 - Both monoclonal T cell-specific antibodies and multivalent major histocompatibility complex proteins are used as diagnostic reagents for T cell-mediated diseases. However, their widespread use as vehicles for drug delivery has been hindered by the lack of versatile methods that couple the targeting potential of these reagents with drugs of clinical relevance. To address this problem, we engineered a multivalent nanoscopic drug carrier that flexibly tethers to a variety of T-cell antigens. Our carriers bound their target T cells specifically and with enhanced sensitivities as compared with free antigen. Additionally, they consistently inhibited the proliferation of the target T cells in vitro and in vivo, whereas drug-free constructs elicited strong stimulation of the target populations. As a result of the flexibility of incorporating multivalent antigen and drug, these carriers have wide potential use as sensitive T-cell detection reagents as well as promising immunostimulatory or immunosuppressive tools.
AB - Both monoclonal T cell-specific antibodies and multivalent major histocompatibility complex proteins are used as diagnostic reagents for T cell-mediated diseases. However, their widespread use as vehicles for drug delivery has been hindered by the lack of versatile methods that couple the targeting potential of these reagents with drugs of clinical relevance. To address this problem, we engineered a multivalent nanoscopic drug carrier that flexibly tethers to a variety of T-cell antigens. Our carriers bound their target T cells specifically and with enhanced sensitivities as compared with free antigen. Additionally, they consistently inhibited the proliferation of the target T cells in vitro and in vivo, whereas drug-free constructs elicited strong stimulation of the target populations. As a result of the flexibility of incorporating multivalent antigen and drug, these carriers have wide potential use as sensitive T-cell detection reagents as well as promising immunostimulatory or immunosuppressive tools.
KW - Peptide-loaded major histocompatibility complex
KW - Polyamidoamine dendrimer
KW - Polyethylene glycol
KW - Streptavidin
KW - T-cell receptor
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U2 - 10.1016/j.nano.2006.11.010
DO - 10.1016/j.nano.2006.11.010
M3 - Article
C2 - 17379171
AN - SCOPUS:33947233339
SN - 1549-9634
VL - 3
SP - 75
EP - 85
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 1
ER -