Peptide-pulsed dendritic cells have superior ability to induce immune-mediated tissue destruction compared to peptide with adjuvant

• Published in: PloS one Vol. 9; no. 3; p. e92380
• Main Authors: Dissanayake, Dilan, Murakami, Kiichi, Tran, Michael D, Elford, Alisha R, Millar, Douglas G, Ohashi, Pamela S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.03.2014; Public Library of Science (PLoS)
• Subjects: Adjuvants; Adjuvants, Immunologic - pharmacology; Animals; Antigenic determinants; Antigens; Biology and Life Sciences; Breast cancer; Cancer; Cancer immunotherapy; Cancer vaccines; CD8 antigen; Cell activation; Cells, Cultured; Clinical trials; Comparative analysis; Cytokines; Cytolysis; Cytolytic activity; Cytotoxicity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Destruction; Diabetes; Diabetes mellitus; Epitopes; Gene expression; Genetic engineering; Health aspects; Health care networks; Humans; Immunodominance; Immunology; Immunotherapy; Laboratories; Lymphocytes T; Medical research; Melanoma; Mice; Pancreas; Peptides; Peptides - pharmacology; Research and Analysis Methods; Rodents; Systematic review; T cell receptors; T cells; T-Lymphocytes, Cytotoxic - immunology; Transgenic animals; Tumors; Vaccination; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092380

Vaccines for cancer immunotherapy are of interest but in general have not yet achieved the desired therapeutic efficacy in clinical trials. We present here a novel model to evaluate vaccine strategies by following tissue destruction in a transgenic model, where a defined antigen is expressed on pancreatic islets. We found that the transfer of syngeneic antigen-pulsed dendritic cells (DCs) resulted in autoimmune cytotoxic T-lymphocyte activation that was not observed following vaccinations that were based on peptides and adjuvants. Importantly, the induction of diabetes by DC transfer is dependent upon the maturation of DCs prior to transfer. Furthermore, diabetes induction only occurred if DCs were pulsed with the immunodominant epitope in addition to at least one other peptide, suggesting greater cytolytic activity upon engagement of multiple T-cell specificities. While the tumor environment undoubtedly will be more complex than healthy tissue, the insights gained through this model provide useful information on variables that can affect CD8-mediated tissue cytolysis in vivo.