Synthetic and immunological studies on clustered modes of mucin-related Tnand TF O-linked antigens: The preparation of a glycopeptide-based vaccine for clinical trials against prostate cancer

The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, hav e been achieved using glycal assembly and cassette methodologies. These syn thetic antigens were subsequently clustered (c) and immunoconjugated to a c arrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunologi cal study. Three Tn conjugates were used to vaccinate groups of mice, and a ll preparations proved to be immunogenic. The Tn(c) covalently linked to KL H (27-KLH) plus the adjuvant QS-21 was the optimal vaccine, inducing high m edian IgM and IgG titers against Tn(c) by ELISA. These antibodies were stro ngly reactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancer cell Line LS-B by FAGS. The antibodies ' reactivities with natural antigens were inhibited with synthetic Tn(c) bu t not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLH and 30-pam plus QS-21 are being tested in patie nts with prostate cancer.