Immunogenicity of synthetic conjugates of Lewis(y) oligosaccharide with proteins in mice: Towards the design of anticancer vaccines Journal Article
| Authors: | Kudryashov, V.; Kim, H. M.; Ragupathi, G.; Danishefsky, S. J.; Livingston, P. O.; Lloyd, K. O. |
| Article Title: | Immunogenicity of synthetic conjugates of Lewis(y) oligosaccharide with proteins in mice: Towards the design of anticancer vaccines |
| Abstract: | Many human carcinomas overexpress the Lewis(y) (Le(y)) blood-group epitope [Fucα1→2Galβ1→4 (Fucα1→3)GlcNAcβ1→3Gal-]. With a view to developing Le(y) based vaccines we have examined the immunogenicity of Le(y)- protein conjugates in mice. Le(y) pentasaccharide was synthesized as its allyl glycoside and coupled to keyhole limpet hemocyanin (KLH) by reductive amination or by a novel method utilizing a maleido-derivitized alkyl carboxyhydrazide as a bridging group to 2-iminothiolane-derivitized KLH. Le(y) oligosaccharide was also coupled to bovine serum albumin by reductive amination. Immunization of groups of mice with the three conjugates, together with the immunological adjuvant QS21, showed that Le(y) oligosaccharide directly coupled to KLH was the most efficient conjugate for eliciting IgG and IgM antibody responses to naturally occurring forms of Le(y) epitopes carried on mucins and glycolipids. These antibodies were also reactive with and cytotoxic to a human breast cancer cell line expressing Le(y) (MCF-7). These experiments suggest that Le(y)-KLH antigen and QS21 adjuvant could be considered as an immunogenic therapeutic vaccine in carcinoma patients. |
| Keywords: | human cell; nonhuman; mouse; animals; mice; immunoreactivity; mice, inbred balb c; immunoglobulin g; cancer vaccines; immunogenicity; antibody response; cancer immunization; tumor cell line; lymphoma; immunological adjuvant; serum albumin, bovine; cross reaction; carbohydrate sequence; complement dependent cytotoxicity; keyhole limpet hemocyanin; hemocyanin; immunoglobulin m; lewis blood-group system; immunization; oligosaccharide; qs 21; cancer antibody; tumor immunology; conjugate; blood group lewis system; glycoconjugates; humans; human; female; priority journal; article; lewis(y) antigen; immune adherence; antitumor vaccine |
| Journal Title: | Cancer Immunology, Immunotherapy |
| Volume: | 45 |
| Issue: | 6 |
| ISSN: | 0340-7004 |
| Publisher: | Springer |
| Date Published: | 1998-01-01 |
| Start Page: | 281 |
| End Page: | 286 |
| Language: | English |
| DOI: | 10.1007/s002620050444 |
| PUBMED: | 9490197 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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15Kudryashov -
144Ragupathi -
539Danishefsky -
228Livingston -
163
Lloyd
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