Bioconjugate Strategies for the Induction of Antigen-Specific Tolerance in Autoimmune Diseases

Abstract

Antigen-specific immunotherapy (ASI) holds great promise for the treatment of autoimmune diseases. In mice, administration of major histocompatibility complex (MHC) binding synthetic peptides which modulate T cell receptor (TCR) signaling under subimmunogenic conditions induces selective tolerance without suppressing the global immune responses. However, clinical translation has yielded limited success. It has become apparent that the TCR signaling pathway via synthetic peptide antigen alone is inadequate to induce an effective tolerogenic immunity in autoimmune diseases. Bioconjugate strategies combining additional immunomodulatory functions with TCR signaling can amplify the antigen-specific immune tolerance and possibly lead to the development of new treatments in autoimmune diseases. In this review, we provide a summary of recent advances in the development of bioconjugates to achieve antigen-specific immune tolerance in vivo, with the discussion focused on the underlying design principles and challenges that must be overcome to target these therapies to patients suffering from autoimmune diseases.

Multicomponent peptide assemblies

“…Often, protein and peptide immunomodulatory agents can bind and affect antigen-specific T-cell surface receptors to elicit autoimmune responses. 430–432 These hydrogels were investigated for their effectiveness as vaccines in mice due to their similar helical structure to fimbrial antigens that elicit T-cell response. Injections of Fmoc-FF/PLL hydrogels were found to activate auto-immune responses through T-cell recognition of specific geometrically defined fibers raising antitumor activity in vivo in tumor-bearing mice.…”

Vaccination by Two DerG LEAPS Conjugates Incorporating Distinct Proteoglycan (PG, Aggrecan) Epitopes Provides Therapy by Different Immune Mechanisms in a Mouse Model of Rheumatoid Arthritis

“…Immunomodulation of the disease promoting pro-inflammatory responses is a potential alternative to current therapies for RA [ 5 , 6 , 7 ]. Rosenthal et al [ 3 ] reviewed and discussed other therapies for RA in relation to LEAPS conjugates and the differences in mechanism of action and targets.…”

Detection of Biothiols with a Fast‐Responsive and Water‐Soluble Pyrazolone‐Based Fluorogenic Probe

“…tion followed by a fast intramolecular thio-Michael addition (Scheme 1A). [22,23] Inspired by this work, we designed a pyrazolone-based Michael acceptor 1 as a fluorogenic probe, composed of a coumarin dye whose fluorescence would be quenched by an intramolecular charge transfer (ICT) and/or photoisomerization process (Scheme 1B). Upon conjugate addition of environmental thiols to 1, a disruption of this fluorescence quenching mechanism would be expected, restoring thus the fluorescence of the coumarin dye.…”