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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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC3117616 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Synthetic and immunological studies of 5'-N-phenylacetyl sTn to develop carbohydrate-based cancer vaccines and to explore the impacts of linkage between carbohydrate antigens and carrier proteins.

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