Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival

Bahmani, Baharak; Uehara, Mayuko; Jiang, Liwei; Ordikhani, Farideh; Banouni, Naima; Ichimura, Takaharu; Solhjou, Zhabiz; Furtmüller, Georg J.; Brandacher, Gerald; Álvarez, David; Andrian, Ulrich H. von; Uchimura, Kenji; Xu, Qiaobing; Vohra, Ishaan; Yilmam, Osman A.; Haik, Yousef; Azzi, Jamil; Kasinath, Vivek; Bromberg, Jonathan S.; McGrath, Martina M.; Abdi, Reza

doi:10.1172/jci120923

Cited by 69 publications

(74 citation statements)

References 77 publications

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“…2019, 6,1900101 HA-NP CD44 and TLR4 on macrophages - [295] Dextran-dexamethasone prodrug Lectin and scavenger receptor on macrophages Esterase [44] Au NP IL-4 -- [296] MSNP IL-4 -- [297] MTC cross-linked with miRNA-146b Mannose receptor on BMDMs - [298] Silica nanoparticle conjugated with KGM -Mannose receptor on BMDMs - [299] RGD-coated Au NP protected by a magnetic nanocage -- [300] Modulation of Tregs Au NP Hyperforin -- [301] Au NP Hexapeptide -- [302] PLGA NP Protein or peptide antigens and rapamycin -- [303] PLA-PLGA NP PLP and rapamycin -- [304] Porous silicon nanoparticle Rapamycin and OVA peptide CD11c on DCs - [36] PLGA NP Anti-CD3 Ab PNAd on HEV - [42] PLGA NP Diabetogenic peptide -- [305] Iron oxide nanoparticle T1D-relevant peptide-MHC class I complexe -- [306] Iron oxide nanoparticle Diabetogenic antigen peptide-MHC class II complex -- [307] PLGA NP IL-2 and TGF-β Biotin on CD4+ T cells - [308] Obesity increases the M1 macrophage infiltration in adipose tissue and promotes the secretion of pro-inflammatory cytokines, such as TNF-α and IL-6, which lead to high risk of glucose intolerance and insulin resistance. Sci.…”

Section: Modulation Of Macrophagesmentioning

confidence: 99%

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Immunomodulatory Nanosystems

et al. 2019

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Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off‐target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provides the most recent advances of nanotechnology for immunostimulation and immunosuppression. In cancer immunotherapy, nanosystems play an essential role in immune cell activation and tumor microenvironment modulation, as well as combination with other antitumor approaches. In infectious diseases, many encouraging outcomes from using nanomaterial vaccines against viral and bacterial infections have been reported. In addition, nanoparticles also potentiate the effects of immunosuppressive immune cells for the treatment of inflammatory and autoimmune diseases. Finally, the challenges and prospects of applying nanotechnology to modulate immunotherapy are discussed.

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Section: Modulation Of Macrophagesmentioning

confidence: 99%

“…[338] Studies employing exogenous neoantigen in tumor vaccine showed strong immune response against cancer. [42] Copyright 2018, American Society for Clinical Investigation. [135] In another study, the tumor neoantigen-coding mRNA delivered by liposomes was efficiently captured by lymphoid-resident Adv.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Immunomodulatory Nanosystems

et al. 2019

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“…Bahmani et al demonstrated this in murine cardiac allografts. 91 They targeted their therapy through the knowledge that peripheral node addressin (PNAd) molecules are uniquely expressed in the high endothelial venule. PNAd is recognized by MECA79 monoclonal antibodies (mAb).…”

Section: Improving Graft Acceptancementioning

confidence: 99%

Applied Bioengineering in Tissue Reconstruction, Replacement, and Regeneration

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et al. 2019

Tissue Engineering Part B: Reviews

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To this day, tissue reconstruction and replacement to address extensive tissue defects due to trauma, tumor resection, genetic and/or chronic diseases, or excessive debridement present a major clinical challenge. Traditional reconstructive techniques most commonly utilize autologous tissue. Undoubtedly, autologous composite tissue transfers or ''flaps,'' skin grafts, as well as the harvesting of bone and/or cartilage have substantially improved the health, functional, and aesthetic outcomes of millions of patients. Unfortunately, these procedures are not without their drawbacks. These include increased operative time, complexity, cost, limited availability of qualitative autologous tissue, wound healing complications, tissue flap failure, and substantial donor-site morbidity. Recently, collaborative research teams-consisting of surgeons, scientists, and engineers-have made substantial progress in their attempts to solve these problems. This article provides historical perspective, covers the major limitations of current standards of care, and reviews recent advances and future prospects in applied bioengineering in the context of tissue reconstruction, replacement, and regeneration.

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“…This is clinically driven by the need to prevent chronic allograft dysfunction and minimise the long‐term side effects of immunosuppression . In this regard, the increased presence of regulatory T cells (Treg cells) within the peripheral circulation and graft microenvironment has been identified as being important in inducing graft tolerance . These cells are a part of the adaptive immune system and are considered to have key roles in immunosuppression and homeostasis in different disease settings …”

Section: Introductionmentioning

confidence: 99%

“…1 In this regard, the increased presence of regulatory T cells (Treg cells) within the peripheral circulation and graft microenvironment has been identified as being important in inducing graft tolerance. [2][3][4] These cells are a part of the adaptive immune system and are considered to have key roles in immunosuppression and homeostasis in different disease settings. 5,6 Regulatory T cells in the peripheral circulation are characterised as CD4 + with high levels of IL-2 receptor alpha chain (CD25 high ) and low levels of CD127 and intracellularly, expressing the forkhead box P3 transcription factor (FOXP3 + ).…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cells in solid organ transplantation

et al. 2020

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The induction of graft tolerance remains the holy grail of transplantation. This is important as chronic allograft dysfunction and the side effects of immunosuppression regimens place a major burden on the lives of transplant patients and their healthcare systems. This has mandated the need to understand the immunobiology of graft rejection and identify novel therapeutics. Regulatory T (Treg) cells play an important role in modulating pro‐inflammatory microenvironments and maintaining tissue homeostasis. However, there are fundamental unanswered questions regarding Treg cell immunobiology. These cells are a heterogeneous entity with functionally diverse roles. Moreover, the adoption of novel deeper immunophenotyping and genomic sequencing technologies has identified this phenotype and function to be more complex than expected. Hence, a comprehensive understanding of Treg cell heterogeneity is needed to safely and effectively exploit their therapeutic potential. From a clinical perspective, the recent decade has seen different clinical teams commence and complete first‐in‐man clinical trials utilising Treg cells as an adoptive cellular therapy. In this review, we discuss these trials from a translational perspective with an important focus on safety. Finally, we identify crucial knowledge gaps for future study.

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Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival

Cited by 69 publications

References 77 publications

Immunomodulatory Nanosystems

Immunomodulatory Nanosystems

Applied Bioengineering in Tissue Reconstruction, Replacement, and Regeneration

Regulatory T cells in solid organ transplantation

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