Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway

Efficient Ag presentation is essential to induce effective cellular and hum oral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broa d immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an e xogenous Ag to efficiently induce both humoral and cellular immunity. The p rinciple of this strategy is illustrated by genetically modifying DCs to se crete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Bg as an exogenous Ag after receptor-mediated internaliz ation for MHC class I and II presentation. Vigorous Ag-specific CD4(+) help er and CD8(+) cytotoxic T cell, as well as B cell, responses were induced b y the transduced DCs in mouse models, Thus, this novel strategy uses a rece ptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vacci nes and immunotherapies.