Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells

The goal of tumor immunotherapy is to elicit immune responses against autol ogous tumors. It would be highly desirable that such responses include mult iple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-pr iming. That is, one could load the DC with tumor lines of any human histoco mpatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from m onocytes and loaded with killed melanoma cells prime naive CD45RA(+)CD27(+) CD8(+) T cells against the four shared melanoma antigens: MAGE-3, gp100, ty rosinase, and MART-1. HLA-A201(+) naive T cells primed by DCs loaded with H LA-A201(-) melanoma cells are able to kill several HLA-A201(+) melanoma tar gets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obta ined with cells from metastatic melanoma patients. This demonstration of cr oss-priming against shared tumor antigens builds the basis for using alloge neic tumor cell lines to deliver tumor antigens to DCs for vaccination prot ocols.