Transfection of dendritic cells with RNA induces CD4- and CD8-mediated T cell immunity against breast carcinomas and reveals the immunodominance of presented T cell epitopes.
Transfection of dendritic cells (DC) with tumor-derived RNA has recently been shown to elicit tumor-specific CTL capable of recognizing and lysing a variety of tumor cells. In our study we analyzed the induction of HLA class I- and II-restricted T cell responses against MCF-7 breast cancer cells. Using this approach we were able to elicit CD4- and CD8-mediated antitumor responses. The CTL specifically lysed MCF-7 cells and DC electroporated with MCF-7 RNA, but spared control cell lines. The specificity of the cytotoxic activity was confirmed in cold target inhibition assays and using mAbs blocking HLA class I molecules. Interestingly, these polyclonal cytotoxic T cells recognized selectively two epitopes derived from the MUC1 and Her-2/neu tumor Ags. The induced Th cells were found to be entirely HLA class II restricted and showed a significant cross-reactivity to a renal cell carcinoma cell line, similar to the results obtained with cytotoxic T cells.
Müller
Martin R
MR
Department of Hematology, Oncology, and Immunology, University of Tübingen, Tübingen, Germany.
Grünebach
Frank
F
Nencioni
Alessio
A
Brossart
Peter
P
D017951:Antigen Presentation / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D016056:Immunodominant Epitopes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D018396:Mucin-1; D010446:Peptide Fragments; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C116055:MUC1 tandem repeat peptide