Immunization of chimpanzees with tumor antigen MUC1 mucin tandem repeat peptide elicits both helper and cytotoxic T-cell responses

CTLs and antibody responses to the tumor-associated antigen MUC1 mucin can be detected in patients with adenocarcinomas of the breast, pancreas, colon , and ovary. However, neither response is generally effective at controllin g disease. Methods to augment immunity to MUC1 are being designed, with the expectation that this,will lead to an antitumor response. The key to elici ting potent immunity to tumor MUC1 may be in generating MUC1-specific T-hel per cell responses, which, to date, have not been reported in cancer patien ts. We have recently demonstrated that a synthetic vaccine representing fiv e copies of the MUC1 tandem repeat peptide can be used to prime MUC1-specif ic human CD4(+) T cells in vitro. Here, we extend these studies to test the immunogenicity and safety of the tandem repeat peptide in the chimpanzee, which has the identical MUC1 tandem repeat sequence to the human. To promot e induction of Th1-type responses, we used the novel adjuvant LeIF, a Leish mania-derived protein that is known to stimulate human peripheral blood mon onuclear cells (PBMCs) and antigen-presenting cells, to produce a Th1-type cytokine profile. We found that MUC1 tandem repeat peptide administered wit h LeIF elicited positive, albeit transient, proliferative T-cell responses to MUC1 in the PBMCs from four of four chimpanzees. Immunization induced MU C1-specific IFN-gamma but not interleukin 4 expression in CD4(+) T cells fr om PBMCs and draining lymph nodes. MUC1-specific CTLs were also generated t hat did not induce detectable autoimmune dysfunction during the 1 year of o bservation, We conclude that the MUC1 tandem repeat peptide can be used to elicit both T-helper and cytotoxic cell responses to MUC1 in the primate an d holds promise as a safe and effective cancer vaccine.