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Synthetic and Immunological Studies of sTn Derivatives Carrying Substituted Phenylacetylsialic Acids as Cancer Vaccine Candidate

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journal contribution
posted on 12.05.2011 by Qianli Wang, Zhongwu Guo
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.