A PHASE-I TRIAL OF A SYNTHETIC MUCIN PEPTIDE VACCINE INDUCTION OF SPECIFIC IMMUNE REACTIVITY IN PATIENTS WITH ADENOCARCINOMA

We tested a 105 amino acid synthetic mucin MUC-1 peptide that has 5 re peated immunodominant epitopes to evaluate toxicity and detect mucin-s pecific immune responses in patients with adenocarcinoma. We also stud ied the enhancement of these responses by vaccinating patients with th e synthetic mucin peptide admired with BCG. Mucins are glycoproteins p resent on the luminal surface of ductal epithelial cells and on turner s derived ham them. The MUC-1 mucin is hypoglycosylated and nonpolariz ed on tumors and this exposes epitopes that can stimulate cytotoxic T- Cells (CTL). We vaccinated 63 patients with 100 mu g of the 105aa muci n peptide mixed with BCG. Two additional vaccinations were given at 3- week intervals. All patients were able to tolerate vaccination, with m ost experiencing local ulceration at the vaccination site. All patient s underwent hypersensitivity (DTH) testing with the 105aa and shorter mucin peptides, prior to vaccination. DTH responses were evaluated at 48 hr and the sites of highest peptide concentration were biopsied. On ly 3 patients had a strong skin response to the long peptide. Examinat ion of 55 biopsies showed intense T-Cell infiltration in 37 patients a nd lesser infiltration in 7. Seven of 22 patients tested had a 2- to 4 -fold increase in mucin-specific CTLp. Serum levels of IL-6 were measu red sequentially using the B9 hybridoma bioassay. Increasing serum lev els of IL-6 correlated with constitutional symptoms (significance 0.00 1) and hypoalbuminemia (significance 0.007) but not with the extent of skin breakdown at vaccination sites. We conclude that mucin Vaccinati on is safe and might serve to enhance specific responses to tumor anti gens, IL-6 may be responsible for the constitution symptoms and hypoal buminemia in these patients. (C) 1996 Academic Press, Inc.