We tested a 105
amino acid synthetic
mucin MUC-1
peptide that has 5 repeated
immunodominant epitopes to evaluate toxicity and detect
mucin-specific immune responses in patients with
adenocarcinoma. We also studied the enhancement of these responses by vaccinating patients with the synthetic
mucin peptide admixed with BCG.
Mucins are
glycoproteins present on the
luminal surface of ductal epithelial cells and on
tumors derived from them. The MUC-1
mucin is hypoglycosylated and nonpolarized on
tumors and this exposes
epitopes that can stimulate cytotoxic T-Cells (CTL). We vaccinated 63 patients with 100 micrograms of the 105aa
mucin peptide mixed with BCG. Two additional vaccinations were given at 3-week intervals. All patients were able to tolerate vaccination, with most experiencing local ulceration at the vaccination site. All patients 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. Only 3 patients had a strong skin response to the long
peptide. Examination of 55 biopsies showed intense T-Cell infiltration in 37 patients and 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 measured sequentially using the B9 hybridoma bioassay. Increasing serum levels of
IL-6 correlated with constitutional symptoms (significance 0.001) and
hypoalbuminemia (significance 0.007) but not with the extent of skin breakdown at vaccination sites. We conclude that
mucin vaccination is safe and might serve to enhance specific responses to
tumor antigens.
IL-6 may be responsible for the constitution symptoms and
hypoalbuminemia in these patients.