SPID#: 12 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 B 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. EBV-immortalized B lymphoblastoid cell lines (B-LCL) were derived from two chimpanzees, transfected with the MUC1 cDNA and treated with an inhibitor of glycosylation in order to expose the relevant tumor associated epitopes. One cell line was also transduced with a retroviral vector containing IL-2 cDNA and produced low levels of IL-2. Cellular and humoral anti-mucin immune responses were evaluated before vaccination and after each boost by limiting dilution analysis and ELISA assays. Delayed type hypersensitivity (DTH) reaction was measured after the last boost. While no mucin specific antibody or T cells were present prior to vaccination, already after the first injection we found measurable CTL frequency in the peripheral blood and an even higher mucin specific CTL frequency in the lymph nodes draining the vaccination site. The intensity of the response differed between the two animals. Mucin specific DTH was also observed. The vaccine did not elicit antibody responses in either animal. MUC-1 is a self-antigen in the chimpanzee and the anti-mucin immune response can be considered an autoimmune response. Yet, long term observation of the two animals yielded no signs of adverse effects of this immunization.
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