In vivo reprogramming of immune cells: Technologies for induction of antigen-specific tolerance

Abstract

Technologies that induce antigen-specific immune tolerance by mimicking naturally occurring mechanisms have the potential to revolutionize the treatment of many immune-mediated pathologies such as autoimmunity, allograft rejection, and allergy. The immune system intrinsically has central and peripheral tolerance pathways for eliminating or modulating antigen-specific responses, which are being exploited through emerging technologies. Antigen-specific tolerogenic responses have been achieved through the functional reprogramming of antigen-presenting cells or lymphocytes. Alternatively, immune privileged sites have been mimicked using biomaterial scaffolds to locally suppress immune responses and promote long-term allograft survival. This review describes natural mechanisms of peripheral tolerance induction and the various technologies being developed to achieve antigen-specific immune tolerance in vivo. As currently approved therapies are non-specific and carry significant associated risks, these therapies offer significant progress towards replacing systemic immune suppression with antigen-specific therapies to curb aberrant immune responses.

Syngeneic red blood cell–induced extracellular vesicles suppress delayed‐type hypersensitivity to self‐antigens in mice

“…This promotes the development of autoimmunity, drawing attention to the clinical importance of newly elaborated methods that enable the preservation or restoration of immune regulatory cell activity. Some of the currently investigated approaches are based on the observation that antigen coupled to autologous cells induces tolerance rather than effector responses . Accordingly, autologous erythrocytes were proposed to constitute good carriers of antigens to induce specific Treg cells …”

“…Some of the currently investigated approaches are based on the observation that antigen coupled to autologous cells induces tolerance rather than effector responses. 4 Accordingly, autologous erythrocytes were proposed to constitute good carriers of antigens to induce specific Treg cells. 5 Along these lines, recent findings revealed that intravenous administration of a high dose of syngeneic mouse red blood cells (sMRBC) coupled with hapten or protein antigen induces CD8 + suppressor T (Ts) cells in mice.…”

Improving Vaccine and Immunotherapy Design Using Biomaterials

“…Model systems of tolerance are being used to generate insights that can then be applied to different diseases [74]. In one example, PLGA NPs were used for intravenous and subcutaneous delivery of rapamycin to induce tolerance against coadministered model antigens [75].…”

Biohybrid Nanoparticles to Negotiate with Biological Barriers

“…As innate immunity members, APCs are responsible not only as an initial nonspecific line of defense, but also to present the antigens derived from self or nonself sources. This capability has made them intriguing targets in autoimmunity and cancer . Here, we review the cross‐talk of some innate immunity cells, and possible inspirations for designing biohybrid NPs.…”