title: Synthetic and Immunological Studies of sTn Derivatives Carrying 5-N-(p-Substituted Phenylacetyl)Sialic Acid for the Development of Effective Cancer Vaccines.
abstract: To search for effective cancer vaccines based on sTn, a sialylated tumor-associated carbohydrate antigen (sialo-TACA) expressed by a number of tumors, four unnatural N-acyl sTn derivatives, including 5'-N-p-methylphenylacetyl sTn (sTnNMePhAc), 5'-N-p-methoxylphenylacetyl sTn (sTnNMeOPhAc), 5'-N-p-acetylphenylacetyl sTn (sTnNAcPhAc) and 5'-N-p-chlorophenylacetyl sTn (sTnNClPhAc), as well as their protein conjugates, were synthesized by a highly convergent procedure. The immunological properties of these sTn derivatives in the form of keyhole limpet hemocyanin conjugate were evaluated in mice and compared to that of sTnNPhAc, a sTn derivative previously investigated as a vaccine candidate. It was shown that sTnNMePhAc, sTnNMeOPhAc, sTnNAcPhAc and sTnNClPhAc are all much more immunogenic than sTnNPhAc and that they provoked strong T cell-dependent IgG1 immune responses useful for cancer immunotherapy. It was concluded that sTnNClPhAc is a promising candidate for cancer vaccine development and is worthy further investigation.
authors.affiliation: Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, USA.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Guo