Study of anti cancer vaccine by using Globo H combined with p-nitrophenyl group
Date Issued
2010
Date
2010
Author(s)
Lee, Hsin-Yu
Abstract
Most of the cancer cells expressed large amounts of carbohydrate antigens on the cell surface. For example, an antigenic hexasaccharide, Globo H (Fucα1→2Galβ1→ 3GalNAcβ1 → 3Galα1→4Galβ1→4Glc), is overexpressed in surfaces of many human cancers, including breast, prostate, ovary, pancreas, colon and lung cancers. It was previously demonstrated that BSA-conjugated Globo H(GH-BSA) adjuvanted with α-GalCer can induce Globo H-specific antibodies. Another study led by Schultz showed that the incorporation of a p-nitrophenylalanine onto TNF can induce a potent antibody response in mice. Herein, we further linked Globo H to p-nitrophenyl group and the resulting unit was conjugated to BSA (GHN-BSA) and explored its immune-eliciting ability as a cancer vaccine. Animal experiments showed that antibodies induced by GHN-BSA vaccine recognized the p-nitrophenyl group but not Globo H carbohydrate antigen. On the other hand, antibodies induced by GH-BSA vaccine recognize Globo H and analogues. We hypothesized that since the p-nitrophenyl group is a strong immunogen and Globo H is a weak one, the same proportion of Globo H to pNO2Phe in the vaccine candidate GHN-BSA would lead to much more antibodies for pNO2Phe. Hence, a new generation of GHN-BSA vaccine with ratio of Globo H over pNO2Phe is 3.78 was synthesized and immunization experiments are ongoing. We wished that raising the ratio of Globo H over pNO2Phe may be able to enhance antibodies specifically to recognize Globo H antigen.
Subjects
breast cancer
vaccine
glycolipid
adjuvants
Globo H
SDGs
Type
thesis
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