Preparation of a divalent cancer vaccine of Globo H and SSEA4
Date Issued
2016
Date
2016
Author(s)
Tseng, Tzu-En
Abstract
Globo-H has been found expressed on cancer cells and also cancer stem cells, but not expressed in normal cells. Recently, more than 16 different types of cancers have been found Globo-H positive, including 60-65% breast cancers. Therefore, Globo-H vaccine should have highly selective and efficient toward various cancers. Moreover, scientists have found that there are SSEA3 and SSEA4 expressed on the surface of cancer cells and also cancer stem cells, and both of SSEA3 and SSEA4 are not found in normal cells. Therefore, Globo-H, SSEA3 and SSEA4 are good antigens as cancer vaccines. There are two generations of Globo-H cancer vaccine under clinical trial. First generation of Globo-H vaccine is Globo-H-KLH vaccine, under phase III clinical trial. Second generation of Globo-H vaccine are Globo-H-DT-QS21 and Globo-H-DT-C34, under phase I clinical trial and preclinical trial respectively. First generation of Globo-H vaccine induces mainly IgM antibodies, which makes it less favorable as a vaccine. However, Globo-H-DT-C34 has been found to have significantly IgG antibodies induced, so it should be a better cancer vaccine. Further studies showed that over 98% of breast cancer patients express at least one of the three carbohydrate, Globo-H, SSEA4 and SSEA3, expressed on surface of cancer cells, so I wanted to make a divalent cancer vaccine of Globo-H and SSEA4.I used para-nitrophenol bifunctional linker to link Globo-H to DT. Afterwards, I used SBAP to attach SSEA4 to Globo-H-DT to afford Globo-H-DT-SSEA4.In another design, I tried to link Globo-H and SSEA4 to an amino acid respectively and then I will use solid phase peptide synthesis technique to control the proportion and distance of Globo-H and SSEA4. However, the following design isn’t finished yet, and I only finished the preparation of Globo-H building block. In sum, a divalent cancer vaccine of Globo-H and SSEA4 could be a new choice of carbohydrate-based cancer vaccines.
Subjects
Globo H
SSEA4
cancer vaccine
carbohydrate-based anti-cancer vaccine
SDGs
Type
thesis
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