Mapping the Mechanical and Immunological Profiles of Polymeric Microneedles to Enable Vaccine and Immunotherapy Applications

Shah, Siddharth; Oakes, Robert S.; Kapnick, Senta M.; Jewell, Christopher M.

doi:10.3389/fimmu.2022.843355

Cited by 19 publications

(15 citation statements)

References 48 publications

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“…Microneedles are a highly modular platform that can be engineered to deliver cargo via surface coating, soluble release, or controlled degradation. [117][118][119][120] In one preliminary study looking at the uptake of pro-insulin, coated stainless steel microneedle delivery was shown to elicit greater antigen-specific activation of cells compared to intradermal injection due to the sustained release from the needles. [121] In a separate study, insoluble T1D autoantigen was conjugated to naturally suppressive gold NPs (Figure 6D), and actively injected into the skin with microneedles.…”

Section: Materials Enable Direct Targeting Of Skin-resident Immune Ce...mentioning

confidence: 99%

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

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Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease‐causing cells. New immunotherapies that induce potent and selective antigen‐specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting—or even reversing—disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen‐specific tolerance and provide commentary on the current state of the clinical development of these technologies.

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Section: Materials Enable Direct Targeting Of Skin-resident Immune Ce...mentioning

confidence: 99%

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

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“…From an immunology perspective, MNs led to similar activation of DCs and did not limit the ability to engage with antigen. [138] Coated stainless steel MNs have also been designed as ID delivery devices for ASITs. In preclinical T1D, stainless steel MNs coated with proinsulin delivered %86% of the therapy into local issue of a NOD mouse model (Figure 5A).…”

Section: Mns Deliver Antigen and Immunomodulatory Cues To Skin-reside...mentioning

confidence: 99%

“…designed a library of polymeric MNs consisting of polymers derived from the extracellular matrix, naturally derived polymers, and synthetic polymers. [ 138 ] Mechanical testing revealed varying stiffness and fracture forces for the MN arrays, with majority of the MNs being able to surpass a minimum fracture force of 4 N, required to penetrate skin. From an immunology perspective, MNs led to similar activation of DCs and did not limit the ability to engage with antigen.…”

Section: Biomaterials Circumvent Various Disadvantages Associated Wit...mentioning

confidence: 99%

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Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Ackun-Farmmer

Jewell

2023

Advanced NanoBiomed Research

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Motivating the Development of Antigen-Specific ImmunotherapiesAutoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CD), and many others develop when the immune system mistakenly recognizes self-antigens as foreign, resulting in an orchestrated attack of host tissues. MS is a demyelinating disease that affects the central nervous system (CNS), RA is a chronic inflammatory joint disorder that can affect other tissues and organs, and T1D is a chronic condition whereby the pancreas produces little or no insulin. Complications from T1D can impact other tissues and organs. CD is a chronic digestive autoimmune disease that is triggered by gluten consumption, resulting in damage to the small intestine. The exact causes of autoimmune diseases are only partially understood. However, biological sex, [1,2] genetics, [3,4] existing autoimmune disease, [5] lifestyle (i.e., smoking, obesity, and exposure), [6][7][8][9][10][11] certain medications, [12] and certain infections [13][14][15][16][17] have been linked with the development of autoimmune diseases. For example, most autoimmune diseases affect more female than male patients, but the reason for this bias is unclear. [1] In MS, risk gene variant, HLA-DRB1*15:01, increases risk for patients, [18] and infection by Epstein-Barr virus (EBV) is associated with increased risks of MS, RA, and other autoimmune diseases. [13][14][15] These are currently no cures for these diseases, creating chronic battles that affect patient quality of life and require life-long compliance. Owing to the complex immunopathology of autoimmune disease, current treatments, even monoclonal antibodies, are not able to distinguish between normal and self-reactive cells. These therapies exploit distinct parenteral (e.g., intravenous [IV], subcutaneous [S.C.], intramuscular (IM), intradermal (ID), transdermal, intranodal) or mucosal (e.g., oral, intranasal (IN), pulmonary, sublingual, ocular) delivery routes to reduce disease severity. [19][20][21][22][23] For example, Ocrelizumab (Ocrevus, Genentech), a recombinant antibody that binds to CD20 on B lymphocytes to treat MS, is administered via IV injection and associated with risk of infections and allergic responses in certain patients. [19] Methotrexate, a first-line disease-modifying antirheumatic drug, is provided orally or S.C. but can lead to liver and lung damage and

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“…This approach has the advantages of delivering a higher density of tolerizing immune signals per mass of administered materials as well as eliminating potentially immunostimulatory effects of the carrier material itself. [59,60] Wilson et al demonstrated carrierfree liver targeting by modifying protein and peptide antigens with polymeric forms of N-acetylgalactosamine (GalNAc) or Nacetylglucosamine (GluNAc), which enable them to bind to Ctype lectins on Kupffer cells, LSECs, and hepatocytes. [53] The authors found that 3 hours after IV administration, synthetically glycosylated ovalbumin (OVA) accumulated in the liver at a 2-fold higher level compared to un-glycosylated OVA.…”

Section: Livermentioning

confidence: 99%

Tissue‐Targeted Drug Delivery Strategies to Promote Antigen‐Specific Immune Tolerance

Yuan

Eppler

Yanes

et al. 2022

Adv Healthcare Materials

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During autoimmunity or organ transplant rejection, the immune system attacks host or transplanted tissue, causing debilitating inflammation for millions of patients. There is no cure for most of these diseases. Further, available therapies modulate inflammation through nonspecific pathways, reducing symptoms but also compromising patients’ ability to mount healthy immune responses. Recent preclinical advances to regulate immune dysfunction with vaccine‐like antigen specificity reveal exciting opportunities to address the root cause of autoimmune diseases and transplant rejection. Several of these therapies are currently undergoing clinical trials, underscoring the promise of antigen‐specific tolerance. Achieving antigen‐specific tolerance requires precision and often combinatorial delivery of antigen, cytokines, small molecule drugs, and other immunomodulators. This can be facilitated by biomaterial technologies, which can be engineered to orient and display immunological cues, protect against degradation, and selectively deliver signals to specific tissues or cell populations. In this review, some key immune cell populations involved in autoimmunity and healthy immune tolerance are described. Opportunities for drug delivery to immunological organs are discussed, where specialized tissue‐resident immune cells can be programmed to respond in unique ways toward antigens. Finally, cell‐ and biomaterial‐based therapies to induce antigen‐specific immune tolerance that are currently undergoing clinical trials are highlighted.

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Mapping the Mechanical and Immunological Profiles of Polymeric Microneedles to Enable Vaccine and Immunotherapy Applications

Cited by 19 publications

References 48 publications

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Tissue‐Targeted Drug Delivery Strategies to Promote Antigen‐Specific Immune Tolerance

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