Genetic Engineering of Dendritic Cells by Adenovirus-Mediated TNF- Gene Transfer

Dendritic cells (DCs) are one of the most potent antigen-presenting cells (APCs). They migrate as precursors from the bone marrow into various organs, where they usually reside in an inactive state (1 ). However, during this regional residency, these cells can efficiently endocytose and process antigens (2 ). Upon activation, they undergo a differentiation process that results in decreased antigen-processing capacity and enhanced expression of major histocompatibility complex (MHC) and costimulatory molecules, after which they migrate to the lymphoid organs to interact with or activate naive T cells (3 ,4 ). Because of the critical roles DCs have in the generation of primary immune responses, an important avenue of investigation is their potential for modulating immunologic functions, such as the induction of immune tolerance or tumor immunity. Recently, it has been shown that DCs pulsed with tumor-derived MHC class I-restricted peptides or tumor lysates are able to induce significant cytotoxic T-lymphocyte (CTL)-dependent antitumor immune responses in vitro as well as in vivo (5 -7 ). However, the therapeutic efficiency of these DC vaccine strategies has been quite limited, because they have protected against rechallenge with only small numbers of parental tumor cells or inhibited very earlystage-established tumors. Thus, a strategic goal of current cancer vaccine research has become the induction of stronger tumor-specific CTL responses.