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.
Russo
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Telethon Institute of Gene Therapy, Istituto Scientifico H.S. Raffaele, 20132 Milan, Italy.
Tanzarella
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S
Dalerba
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Rigatti
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D
Rovere
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P
Villa
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Bordignon
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Traversari
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C
D016475:3T3 Cells; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D019556:COS Cells; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D015235:HLA-B Antigens / Q000276:immunology*; D059950:HLA-B52 Antigen; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015235:HLA-B Antigens; D059950:HLA-B52 Antigen; D015395:Histocompatibility Antigens Class I; C072013:MAGEA3 protein, human; C489519:Mageb3 protein, mouse; D009363:Neoplasm Proteins