Synthetic and Immunological Studies on Clustered Modes of Mucin-Related Tn and TF O-Linked Antigens: The Preparation of a Glycopeptide-Based Vaccine for Clinical Trials against Prostate Cancer
详细信息 查看全文
- 作者：Scott D. Kuduk ; Jacob B. Schwarz ; Xiao-Tao Chen ; Peter W. Glunz ; Dalibor Sames ; Govindaswami Ragupathi ; Philip O. Livingston ; and Samuel J. Danishefsky
- 刊名：Journal of the American Chemical Society
- 出版年：1998
- 出版时间：December 9, 1998
- 年：1998
- 卷：120
- 期：48
- 页码：12474 - 12485
- 全文大小：577K
- 年卷期：v.120,no.48(December 9, 1998)
- ISSN：1520-5126
文摘
The syntheses of two tumor-associated carbohydrate antigens, Tn and TF, have been achieved usingglycal assembly and cassette methodologies. These synthetic antigens were subsequently clustered (c) andimmunoconjugated to a carrier protein (KLH or BSA) or a synthetic lipopeptide (pam) for immunologicalstudy. Three Tn conjugates were used to vaccinate groups of mice, and all preparations proved to beimmunogenic. The Tn(c) covalently linked to KLH (27-KLH) plus the adjuvant QS-21 was the optimalvaccine, inducing high median IgM and IgG titers against Tn(c) by ELISA. These antibodies were stronglyreactive with the Tn(c) positive human colon cancer cell line LS-C but not the Tn(c) negative colon cancercell line LS-B by FACS. The antibodies' reactivities with natural antigens were inhibited with synthetic Tn(c)but not with structurally unrelated compounds. On the basis of these results, vaccines containing 27-KLHand 30-pam plus QS-21 are being tested in patients with prostate cancer.