A nanoscopic multivalent antigen-presenting carrier for sensitive detection and drug delivery to T Cells

Abstract 

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.

Key words: Peptide-loaded major histocompatibility complex, T-cell receptor, Polyethylene glycol, Polyamidoamine dendrimer, Streptavidin