The focus of our work is on the use of dendritic cells (DC) as immunotherapeutic vaccines against melanoma and other malignancies. DC are extremely potent antigen presenting cells (APC) that express MHC class I and class II molecules and an array of costimulatory molecules that are required for the activation of naïve T cells. Thus, DC make ideal candidates as vaccine delivery systems for the generation of immune responses against tumors. Recent studies have demonstrated that many patients make immune responses against their tumors, though they usually ultimately fail to control tumor outgrowth. Extensive investigations have identified many of the proteins that are the targets of these immune responses, and further defined the MHC class I and MHC class II-restricted peptides derived from tumor antigens that are presented to cytotoxic CD8+- and helper CD4+ T cells respectively. DC pulsed with such peptides are the basis of the vaccines that we are currently studying.
Recent studies in our laboratory have indicated that mice immunized with both MHC class I- and class II-restricted peptides derived from an antigen expressed by tumor results in greater control of tumor outgrowth as compared to mice immunized with the MHC class I-restricted peptide alone (Hwang et al, 2007). Further studies have indicated that tumor-specific memory CD4+ T cells enhance the activation, differentiation and, in particular, the infiltration of tumor by secondary CD8+ T cells.