Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

作者：F. Bérard, Patrick Blanco, Jean M. Davoust, Eve-Marie Neidhart-Berard, Mahyar A Nouri-Shirazi, Nicolas Taquet, Donata Rimoldi, J.-C. Cerottini, Jacques Banchereau, Karolina Palucka · 发表于：The Journal of Experimental Medicine · 年份：2000 · DOI：10.1084/jem.192.11.1535 · 被引用次数：286 · 研究领域：Immunotherapy and Immune Responses、CAR-T cell therapy research、vaccines and immunoinformatics approaches

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA(+)CD27(+)CD8(+) T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201(+) naive T cells primed by DCs loaded with HLA-A201(-) melanoma cells are able to kill several HLA-A201(+) melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols.