Most tumors express certain unique or excessive carbohydrates, which are known as tumor-associated carbohydrate antigens (TACAs). TACAs are useful targets for the development of cancer vaccines or immunotherapies. However, TACAs are poorly immunogenic, thus they cannot elicit robust immune responses useful for cancer therapy. To overcome this problem, we have developed a new therapeutic strategy that combines synthetic vaccines made of unnatural sialo-TACA derivatives and metabolic glycoengineering of cancer cell to express unnatural sialo-TACAs. In this regard, we have established a novel strategy of fully synthetic glycoconjugate vaccines with monophosphoryl lipid A (MPLA) as the carrier molecule. These vaccines could induce robust IgG immune responses without the use of an additional adjuvant, suggesting that they are self-adjuvanting and provoke T cell-dependent immunity that is very useful for cancer immunotherapy. We have further demonstrated that cancer cells can be efficiently and selectively glycoengineered by using a monosaccharide to express the unnatural sialo-TACA analog. Our in vivo studies confirmed that immunization using the synthetic vaccine followed by treatment with the unnatural monosaccharide could effectively inhibit tumor growth and metastasis and elongate animal survival.

New type of fully synthetic self-adjuvanting glycoconjugate vaccine

248th National Meeting (2014)

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