Combination Treatment with Antigen-Specific Dual-Sized Microparticle System Plus Anti-CD3 Immunotherapy Fails to Synergize to Improve Late-Stage Type 1 Diabetes Prevention in Nonobese Diabetic Mice

Stewart, Joshua M.; Posgai, Amanda L.; Leon, Juan; Haller, Michael J.; Keselowsky, Benjamin G.

doi:10.1021/acsbiomaterials.0c01075

Cited by 8 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One approach being studied is a dual-sized MP system that delivers a combination of antigens, small molecules, and cytokines to promote tolerogenic APCs for autoimmunity. [64][65][66][67][68][69] This approach takes advantage of the control of MP size to load intracellular cues (antigen, vitamin D3) into small MPs and extracellular cues (TGF-𝛽, granulocyte macrophage-colony stimulating factor) into large MPs. The smaller particles are phagocytosed by target APCs, delivering cargo intracellularly, while the larger particles are too large for phagocytosis, instead releasing cargo into the extracellular space (Figure 3A).…”

Section: Materials Allow For Potent and Targeted Tolerance Induction ...mentioning

confidence: 99%

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

View full text Add to dashboard Cite

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.

show abstract

Section: Materials Allow For Potent and Targeted Tolerance Induction ...mentioning

confidence: 99%

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

View full text Add to dashboard Cite

show abstract

“…Interestingly, this change in GM‐CSF and TGF‐β1 dosing did not offer dramatic protection in NOD T1D mice despite an improvement in the frequency of DCs at the injection site. [ 102 ] In another report, PEGylated PLGA NPs loaded with PLP 139‐151 peptides and Rapamycin (tNPs) significantly reduced paralysis in relapsing‐remitting EAE (RR‐EAE) mice after a single treatment at peak disease compared with single‐cargo controls. [ 84 ] Most importantly, this study showed that tNPs could induce antigen‐specific T REGS, and that transferring splenocytes from EAE‐treated tNP mice could protect naïve mice from getting sick.…”

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

confidence: 99%

“…MPs (%1 μm) are phagocytosed by APCs while larger MPs cannot passively drain to LNs but can interact with cell surface receptors on APCs to induce a distinct desired response. [99][100][101][102] If internalization of MPs or NPs is desired, a negatively charged surface is typically favored owing to reduced aggregation and protein adsorption on the surface. [103] Various preclinical studies using biomaterials focus on S.C. delivery.…”

Section: Polymeric Biomaterials Delivered Subcutaneously Take Advanta...mentioning

confidence: 99%

“…[103] Various preclinical studies using biomaterials focus on S.C. delivery. [99][100][101][102][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120] These therapies combine antigen with immunomodulatory cues (i.e., cytokines, toll-like receptor antagonists, immunosuppressants, etc.) through loading or coupling with NPs and MPs to enable combinatory presentation to relevant immune cells.…”

Section: Polymeric Biomaterials Delivered Subcutaneously Take Advanta...mentioning

confidence: 99%

See 1 more Smart Citation

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

Ackun-Farmmer

Jewell

2023

Advanced NanoBiomed Research

View full text Add to dashboard Cite

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

show abstract

“…In theory, the combination of MP platform and anti-CD3 in the treatment of T1D mice seems to be a good direction. Sadly, there was no therapeutic benefit when considering the combination of biomaterials with CD3 antibodies ( 38 ). In this way, biomaterial combination therapy for T1D can be better utilized.…”

Section: Immune Suppressive Agentsmentioning

confidence: 99%

Leverage biomaterials to modulate immunity for type 1 diabetes

Jing

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The pathogeny of type 1 diabetes (T1D) is mainly provoked by the β-cell loss due to the autoimmune attack. Critically, autoreactive T cells firsthand attack β-cell in islet, that results in the deficiency of insulin in bloodstream and ultimately leads to hyperglycemia. Hence, modulating immunity to conserve residual β-cell is a desirable way to treat new-onset T1D. However, systemic immunosuppression makes patients at risk of organ damage, infection, even cancers. Biomaterials can be leveraged to achieve targeted immunomodulation, which can reduce the toxic side effects of immunosuppressants. In this review, we discuss the recent advances in harness of biomaterials to immunomodulate immunity for T1D. We investigate nanotechnology in targeting delivery of immunosuppressant, biological macromolecule for β-cell specific autoreactive T cell regulation. We also explore the biomaterials for developing vaccines and facilitate immunosuppressive cells to restore immune tolerance in pancreas.

show abstract

Combination Treatment with Antigen-Specific Dual-Sized Microparticle System Plus Anti-CD3 Immunotherapy Fails to Synergize to Improve Late-Stage Type 1 Diabetes Prevention in Nonobese Diabetic Mice

Cited by 8 publications

References 50 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

Leverage biomaterials to modulate immunity for type 1 diabetes

Contact Info

Product

Resources

About