A nanoscopic multivalent antigen-presenting carrier for sensitive detection and drug delivery to T cells.
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.
Fahmy
Tarek M
TM
Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA. tarekfahmy@yale.edu
Schneck
Jonathan P
JP
Saltzman
W Mark
WM
D019264:Adoptive Transfer; D000588:Amines; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles; D010455:Peptides / Q000494:pharmacology; D011092:Polyethylene Glycols; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000588:Amines; D000941:Antigens; D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D010455:Peptides; D011092:Polyethylene Glycols; D004317:Doxorubicin