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Review
. 2018 Feb 20:9:230.
doi: 10.3389/fimmu.2018.00230. eCollection 2018.

Nanoparticles for the Induction of Antigen-Specific Immunological Tolerance

Takashi Kei Kishimoto  1 , Roberto A Maldonado  1
Affiliations
Review

Nanoparticles for the Induction of Antigen-Specific Immunological Tolerance

Takashi Kei Kishimoto et al. Front Immunol. .

Abstract

Antigen-specific immune tolerance has been a long-standing goal for immunotherapy for the treatment of autoimmune diseases and allergies and for the prevention of allograft rejection and anti-drug antibodies directed against biologic therapies. Nanoparticles have emerged as powerful tools to initiate and modulate immune responses due to their inherent capacity to target antigen-presenting cells (APCs) and deliver coordinated signals that can elicit an antigen-specific immune response. A wide range of strategies have been described to create tolerogenic nanoparticles (tNPs) that fall into three broad categories. One strategy includes tNPs that provide antigen alone to harness natural tolerogenic processes and environments, such as presentation of antigen in the absence of costimulatory signals, oral tolerance, the tolerogenic environment of the liver, and apoptotic cell death. A second strategy includes tNPs that carry antigen and simultaneously target tolerogenic receptors, such as pro-tolerogenic cytokine receptors, aryl hydrocarbon receptor, FAS receptor, and the CD22 inhibitory receptor. A third strategy includes tNPs that carry a payload of tolerogenic pharmacological agents that can "lock" APCs into a developmental or metabolic state that favors tolerogenic presentation of antigens. These diverse strategies have led to the development of tNPs that are capable of inducing antigen-specific immunological tolerance, not just immunosuppression, in animal models. These novel tNP technologies herald a promising approach to specifically prevent and treat unwanted immune reactions in humans. The first tNP, SEL-212, a biodegradable synthetic vaccine particle encapsulating rapamycin, has reached the clinic and is currently in Phase 2 clinical trials.

Keywords: immunological tolerance; nanoparticles; rapamycin; regulatory T cells; tolerogenic dendritic cells.

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Figures

Figure 1
Figure 1
Mode of action of tolerogenic nanoparticles (tNPs). Antigen-presenting cells (APCs) play a major function in the immune system by integrating cues from the environment to promote immunity or tolerance. (A) Immunogenic stimuli such as cytokines, microbial components recognized by toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptor (RLR), and changes in the metabolic state of the tissue can activate APCs to induce immunity. (B) At steady-state immature APCs that capture self and innocuous antigens, such as those from commensal bacteria, present antigen in the absence of costimulation to induce or maintain tolerance. (C) Some tolerogenic NPs harness these natural tolerogenic processes by targeting tolerogenic delivery routes (oral tolerance), tolerogenic environments (liver), or mimicking apoptotic cells. (D) Other tNPs actively promote immune tolerance by employing pharmacological agents to induce tolerogenic dendritic cells. (E) Lymphocytes can also be targeted directly by tNPs that engage antigen-specific receptors in absence of costimulation or by targeting tolerogenic receptors. In all cases, tolerance is mediated by the preventing the activation of or eliminating antigen-specific cells both (naïve or effector) and/or the expansion of regulatory lymphocytes.
Figure 2
Figure 2
Different types of tolerogenic nanoparticles according to their content and mechanism of action.
See this image and copyright information in PMC

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