Design, synthesis, and initial immunological evaluation of glycoconjugates based on saponin adjuvants and the Tn antigen

Abstract

Versatile chemical strategy for the development of novel conjugates based on streamlined saponin adjuvants covalently linked to a synthetic antigen (Tn) that induced moderate antibody responses in mice.

Development of synthetic, self-adjuvanting, and self-assembling anticancer vaccines based on a minimal saponin adjuvant and the tumor-associated MUC1 antigen

“…With the above design criteria in mind, we developed a streamlined synthetic strategy to access the multicomponent, self-adjuvanting constructs building upon our optimized, quillaic acid-based saponin adjuvant platform ("QA"). 61,72 Di-component conjugates 4 [QA-MUC1] and 5 [QA-TnMUC1], as well as tri-component Fig. 1 (A) QS-21 is a mixture of isomers comprising four principal domains: a branched trisaccharide, a central triterpene core (quillaic acid), a linear tetrasaccharide terminating in either apiose (1a) or xylose (1b), and a glycosylated diester acyl chain.…”

Saponins of Selected Triterpenoids as Potential Therapeutic Agents: A Review

“…The natural mixture of 11a and 11b ( Figure 11 ) has also been known under the code QS-21 [ 67 ]. The compounds 11c – 11f ( Figure 11 ) were subsequently prepared and immunologically evaluated on the basis of streamlined saponin adjuvants and the Tn (Thomsen-nouveau) carbohydrate antigen [ 68 ]. These synthetic compounds ( 11c – 11f ) induced moderate antibody responses in mice, which initiated a search for optimization in the development of self-adjuvanting glycoconjugate cancer vaccines [ 67 , 68 ].…”

“…The Tn (Thomsen-nouveau) antigen [ N -acetylgalactosamine (GalNAc) α- O -linked to serine or threonine] is a typical tumor-associated carbohydrate antigen (TACA) overexpressed on the cell surface glycoproteins in human tumors [ 67 , 68 ]. Despite its potential for anticancer vaccine development, it is only weakly immunogenic, and needs to be administered as a conjugate to induce strong immune responses [ 68 ].…”

“…The Tn (Thomsen-nouveau) antigen [ N -acetylgalactosamine (GalNAc) α- O -linked to serine or threonine] is a typical tumor-associated carbohydrate antigen (TACA) overexpressed on the cell surface glycoproteins in human tumors [ 67 , 68 ]. Despite its potential for anticancer vaccine development, it is only weakly immunogenic, and needs to be administered as a conjugate to induce strong immune responses [ 68 ]. The classical approach always involved a covalent bond to an immunogenic carrier protein, finally leading to an enhanced antigen presentation, T cell activation, and co-administration with an immunological adjuvant such as the saponin natural products 11a and 11b , which were responsible for activating both antibody and cellular immunity, further strengthening the immune response [ 67 ].…”

“…A modification of the 3β- d -glucuronic acid residue from the Quillaja saponin adjuvants was made by the N -acylation of the carboxyl group by linear alkyl C 8 -, C 10 -, C 12 -, and C 14 -carbon-chained amines [ 67 , 68 ]. The synthesized amide derivatives bear linear alkyl amine chains as substituents of the carboxyl group of the 3β- d -glucuronic acid unit.…”