SPID#: 11 Aberrant glycosylation of the mucin molecule (MUC-1) expressed on epithelial tumors leads to the exposure of novel tumor-associated core protein epitopes which are recognized by tumor specific antibodies and cytotoxic T cells (CTL). Consequently, MUC-1 mucin could be considered a possible target for tumor immunotherapy. A candidate anti-mucin cellular vaccine employing autologous dendritic cells instead of tumor cells for the presentation of tumor associated mucin epitopes was tested in chimpanzees because they express the same molecule with the same sequence and tissue distribution. In preparation for the in vivo studies we obtained blood samples from various animals at the time they were undergoing routine physical examinations. We developed a culture system to grow chimpanzee dendritic cells in vitro. This system was then tested in vivo. Dendritic cells were grown for six days in vitro and then loaded with a mucin synthetic peptide or a control antigen ovalbumin. Autologous antigen loaded dendritic cells were then injected IV, and animals boosted once with antigen in conventional adjuvant TIterMax. Three weeks later blood and lymph nodes were collected and examined for the development of mucin-specific or ovalbumin-specific immune response. We found that dendritic cells were effective at inducing OVA-specific immunity, but not much better than the conventional adjuvant. We saw no immunity generated to the mucin peptide with either regimen, confirming our observations in vitro that this peptide sequence does not contain helper epitopes. We are initiating further studies with whole mucin proteins as well as trafficking of dendritic cells after injection.
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