Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response

In an attempt to transduce monocyte-derived dendritic cells (DCs) with a retroviral vector coding for an intracytoplasmic tumor antigen (TAA), we were confronted by the evident dissociation between the ability of the treated DCs to induce a TAA-specific response, and the presence of integrated vector proviral DNA. The TAA, i.e., MAGE-3, was acquired by DCs and presented to immune effectors, thanks to the property of DCs to uptake the apoptotic bodies released by the irradiated vector-producing cells. Indeed, we observed that upon irradiation vector-producing cells underwent apoptotic cell death, monitored by annexin V and propidium iodide staining, and were phagocytosed by DCs. Lymphocytes obtained from a patient affected by a MAGE-3 ⁺ melanoma, were stimulated in vitro with autologous DCs previously exposed to irradiated MAGE-3-expressing cells. This procedure led to the induction of MAGE-3- specific cytotoxic effectors, directed against a yet unknown MAGE-3 epitope presented by HLA-A*B5201 molecules. These data demonstrate that DCs can present engulfed human TAAs, thus providing strategies for cancer vaccination.