Synthetic and Immunological Studies of sTn Derivatives Carrying Substituted Phenylacetylsialic Acids as Cancer Vaccine Candidate
journal contributionposted on 12.05.2011 by Qianli Wang, Zhongwu Guo
Any type of content formally published in an academic journal, usually following a peer-review process.
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 of further investigation.