Induction of a T Helper Cell Response against the Tumor Associated Antigen Her-2 Using Monocyte-Derived Dendritic Cells

Abstract

In mouse models established tumors can be eradicated by adoptive transfer of T lymphocytes specific for a tumor associated antigen (TAA) (Greenberg, 1986; Shu and Rosenberg, 1985). Serveral clinical studies demonstrated, that T cell and humoral immunity exists in cancer patients indicating the potential of eliciting an adaptive immune response against cancer (Boon et al., 1994; Houghton, 1994). This immune response is based on TAAs released from tumor cells that are ingested by resident dendritic cells (DCs). The antigens are processed by DCs and antigen peptides are presented together with major histocompatibility complex (MHC)-encoded molecules on the surface. Upon antigen uptake DCs mature and migrate to lymphoid tissues. In T cell rich zones the immune response is initiated by the interaction of DCs with naive T cells (Banchereau and Steinman, 1998). The recognition of the peptide-MHC complex by a T cell receptor is the first signal for T cell activation and provides the antigen specificity for the T cell response. The second signal is mediated through the binding of the costimulators CD80 and CD86 to the T cell molecule CD28 (Lenschow et al., 1996). As a consequence antigen-specific T cells proliferate and differentiate into effector T cells. These effector cells enter the circulation and migrate to the sites of antigen challenge (Butcher and Picker, 1996). After antigen contact, the T cells perform their effector functions: CD8⁺ cytolytic T lymphocytes (CTLs) kill target cells. CD4⁺ T helper cells (Th cells) secrete cytokines consecutively providing help for CTLs and B cells (Walter et al., 1995).