Nanomaterials for antigen-specific immune tolerance therapy

Park, Jin-Won; Wu, Yina; Li, Qiaoyun; Choi, Jaehyun; Ju, Hyemin; Cai, Yu-Dong; Lee, Jaiwoo; Oh, Yu‐Kyoung

doi:10.1007/s13346-022-01233-3

Cited by 8 publications

(3 citation statements)

References 170 publications

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“…[25] Inspired by the previous reports that the rapamycin poly(lactic-co-glycolic acid) nanoparticle systems can induce immunological tolerance and inhibit the formation of ADA. [13,26,27] In this study, we synthesized the PEGylated RAPA, which not only increased the solubility of RAPA but also served as drug carrier to encapsulate free RAPA via self-assembly with high drug loading capacity (11%) and pH-sensitive drug release.…”

Section: Discussionmentioning

confidence: 99%

Mitigation of Anti‐Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co‐Injection of Nano‐Rapamycin

Chang,

Xiong,

Zou

et al. 2023

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The induction of anti‐drug antibody (ADA) is a formidable challenge for protein‐based therapy. Trichosanthin (TCS) as a class of ribosome‐inactivating proteins is widely studied in tumor treatment. However, the immunogenicity can induce the formation of ADA, which can cause hypersensitivity reactions and neutralize the efficacy of TCS, thus limiting its clinical application in cancer therapy. Here, a promising solution to this issue is presented by co‐administration of the rapamycin nanoparticles and TCS. PEGylated rapamycin amphiphilic molecule is designed and synthesized as a prodrug and a delivery carrier, which can self‐assemble into a nanoparticle system with encapsulation of free rapamycin, a hydrophobic drug. It is found that co‐injection of the PEGylated rapamycin nanoparticles and TCS could mitigate the formation of anti‐TCS antibody via inducing durable immunological tolerance. Importantly, the combination of TCS and the rapamycin nanoparticles has an enhanced effect on inhibit the growth of breast cancer. This work provides a promising approach for protein toxin‐based anticancer therapy and for promoting the clinical translation.

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Section: Discussionmentioning

confidence: 99%

Mitigation of Anti‐Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co‐Injection of Nano‐Rapamycin

Chang,

Xiong,

Zou

et al. 2023

Small

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“…Nanoparticles (NPs) have risen as a safe and effective technology to induce Ag-specific immune tolerance − and have recently demonstrated success in clinical trials for the treatment of celiac disease. , Antigen-presenting cells (APCs) are popular targets for NP-based immunotherapy. APCs, such as dendritic cells (DC) or macrophages, can process and present NP-delivered Ags to T cells to activate or suppress adaptive immune responses. − Activation of naïve T cells occurs via a three-signal model where (1) processed Ag is presented via major histocompatibility complexes (MHCs) to cognate T cell receptors (TCRs) (signal 1); (2) cosignaling molecules engage with receptors on T cells (signal 2); and (3) these interactions induce the secretion of cytokines (signal 3). ,, The context in which APCs present Ag to T cells is critical for determining T cell phenotypes. , The lack of costimulatory molecule expression in the absence of inflammation (e.g., tissue injury or infection) during Ag presentation to T cells supports the differentiation to regulatory T cell (Treg) or unresponsive T cell (anergy or deletion) activity, , whereas Ag presentation in the presence of inflammatory signals (i.e., costimulation) to T cells supports T cell activation and proliferation. Therefore, manipulating these signals holds great promise for developing Ag-specific immunotherapies to treat various immune disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Delivery of peptide-based Ags using polymer-based NPs has successfully demonstrated the ability to harness peripheral tolerance mechanisms to induce Ag-specific tolerance in vivo. − Notably, the properties of NP Ag carriers can be tuned to enhance safety, efficacy, and tolerogenic properties. , The delivery of Ag has been achieved through surface conjugation to preformed polymer-based NPs [NP-sAg] or encapsulation [NP(Ag)]; however, these methods face several limitations. , Surface conjugation of Ag to NPs can alter their size and charge, leading to increased polydispersity, instability, and antibody-mediated immune recognition. NP(Ag) addresses many of the size and charge concerns of NP-sAg .…”

Section: Introductionmentioning

confidence: 99%

Development of Protein–Polymer Conjugate Nanoparticles for Modulation of Dendritic Cell Phenotype and Antigen-Specific CD4 T Cell Responses

Scotland,

Cottingham,

Lasola

et al. 2023

ACS Appl. Polym. Mater.

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Polymeric nanoparticles (NPs) composed of poly(lactic-co-glycolic acid) (PLGA) have found success in modulating antigen (Ag)-specific T cell responses for the treatment multiple immunological diseases. Common methods by which Ags are associated with NPs are through encapsulation and surface conjugation; however, these methods suffer from several limitations including uncontrolled Ag loading, burst release, and potential immune recognition. To overcome these limitations and study the relationship between NP design parameters and the modulation of innate and Ag-specific adaptive immune cell responses, we developed ovalbumin (OVA) protein-PLGA bioconjugate NPs (acNP-OVA). OVA was first modified by conjugation with multiple PLGA polymers to synthesize the OVA–PLGA conjugates, followed by precise combination with unmodified PLGA to form acNP-OVA with well-defined Ag loadings, reduced burst release, and reduced antibody recognition. Expression of MHC II, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs) increased as a function of acNP-OVA Ag loading. NanoString studies using BMDCs showed that PLGA NPs generally induced anti-inflammatory gene expression profiles independent of the Ag delivery method, where S100a9, Sell, and Ppbp were most significantly reduced. Coculture studies using acNP-OVA-treated BMDCs and OT-II CD4+ T cells revealed that Ag-specific T cell activation, expansion, and differentiation were dependent on Ag loading and formulation parameters. CD25 expression was induced using acNP-OVA with the lowest Ag loading; however, the induction of robust CD4+ T cell proliferative and cytokine responses required acNP-OVA formulations with higher Ag loadings, which was supported using a regulatory T cell (Treg) induction assay. The distinct differences in Ag loading required to achieve various T cell responses supported the concept of an Ag loading threshold for Ag-specific immunotherapy. We anticipate this work will help guide NP designs and aid in the future development of NP-based immunotherapies for Ag-specific immunomodulation.

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