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Synthesis and In Vivo Immunological Evaluation of Novel Saponin–Antigen Conjugates Incorporating Tumor-Associated Carbohydrate and Peptide Epitopes
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DOI：10.1002/chem.71192.png)
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Abstract
En 中文
Subunit cancer vaccines based on aberrant glyglycoproteins or glycolipids overexpressed on the tumor cell surface are limited by the inherent low immunogenicity of the corresponding glycan/peptide antigens. As such, they require the implementation of novel strategies that can boost the induced immune responses. One of these approaches exploits the conjugation of such antigenic fragments to immunoactive molecules, such as adjuvants and immunostimulatory epitopes, leading to unimolecular constructs with self-adjuvanting properties. Herein, we report the development of novel di- and tricomponent conjugates built upon a streamlined, underexploited saponin scaffold derived from the QS-21 adjuvant, which was covalently linked to carbohydrate and peptide antigens found on tumor-associated glycolipids (e.g., Gb3 trisaccharide) and glycoproteins (e.g., Tn antigen and MUC1 tandem repeat sequence). Facile, late-stage conjugation to a T-helper peptide epitope resulted in self-adjuvanting vaccine constructs that induced increased levels of antigen-specific antibodies in mice recognizing the native antigen on cancer cells. The chemical versatility of our synthetically accessible saponin platform, together with the nontoxicity and immunogenicity of these new tricomponent candidates, emphasizes the potential of our novel saponin-based, self-adjuvanting approach for the development of molecular vaccine prototypes with prospective applications in cancer immunotherapy.
Keywords:
cancer vaccines
glycan synthesis
saponin adjuvant
self-adjuvanting glycoconjugates
tumor-associated carbohydrate/glycopeptide antigens
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