Design, Synthesis, and Immunological Evaluation of a Multicomponent Construct Based on a Glycotripeptoid Core Comprising B and T Cell Epitopes and a Toll-like Receptor 7 Agonist That Elicits Potent Immune Responses - Archive ouverte HAL
Article Dans Une Revue Journal of Medicinal Chemistry Année : 2018

Design, Synthesis, and Immunological Evaluation of a Multicomponent Construct Based on a Glycotripeptoid Core Comprising B and T Cell Epitopes and a Toll-like Receptor 7 Agonist That Elicits Potent Immune Responses

Résumé

We present here for the first time the synthesis and immunological evaluation of a fully synthetic three-component anticancer vaccine candidate that consists of a β-glycotripeptoid core mimicking a cluster of Tn at the surface of tumor cells (B epitope), conjugated to the OVA 323–339 peptide (T-cell epitope) and a Toll-like receptor 7 (TLR7) agonist for potent adjuvanticity. The immunological evaluation of this construct and of precursor components demonstrated the synergistic activity of the components within the conjugate to stimulate innate and adaptive immune cells (DCs, T-helper, and B-cells). Surprisingly, immunization of mice with the tricomponent GalNAc-based construct elicited a low level of anti-Tn IgG but elicited a very high level of antibodies that recognize the TLR7 agonist. This finding could represent a potential vaccine therapeutic approach for the treatment of some autoimmune diseases such as lupus.

Domaines

Chimie
Fichier non déposé

Dates et versions

hal-01916386 , version 1 (08-11-2018)

Identifiants

Citer

Thomas Szekely, Olivier Roy, Edith Dériaud, Aurélie Job, Richard Lo-Man, et al.. Design, Synthesis, and Immunological Evaluation of a Multicomponent Construct Based on a Glycotripeptoid Core Comprising B and T Cell Epitopes and a Toll-like Receptor 7 Agonist That Elicits Potent Immune Responses. Journal of Medicinal Chemistry, 2018, 61 (21), pp.9568 - 9582. ⟨10.1021/acs.jmedchem.8b00960⟩. ⟨hal-01916386⟩
66 Consultations
0 Téléchargements

Altmetric

Partager

More