Moving towards personalized treatments of immune-related adverse events

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(8), P. 504 - 515

Published: April 3, 2020

Language: Английский

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Modeling human adaptive immune responses with tonsil organoids

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(1), P. 125 - 135

Published: Jan. 1, 2021

Language: Английский

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Breakthrough treatments for accelerated wound healing

Science Advances, Journal Year: 2023, Volume and Issue: 9(20)

Published: May 17, 2023

Skin injuries across the body continue to disrupt everyday life for millions of patients and result in prolonged hospital stays, infection, death. Advances wound healing devices have improved clinical practice but mainly focused on treating macroscale versus underlying microscale pathophysiology. Consensus is lacking optimal treatment strategies using a spectrum products, which has motivated design new therapies. We summarize advances development novel drug, biologic biomaterial therapies marketed those trials. also share perspectives successful accelerated translation integrated healing.

Language: Английский

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Immune responses to retinal gene therapy using adeno-associated viral vectors – Implications for treatment success and safety

Progress in Retinal and Eye Research, Journal Year: 2020, Volume and Issue: 83, P. 100915 - 100915

Published: Oct. 15, 2020

Language: Английский

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Poor Translatability of Biomedical Research Using Animals — A Narrative Review

Alternatives to Laboratory Animals, Journal Year: 2023, Volume and Issue: 51(2), P. 102 - 135

Published: March 1, 2023

The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been past few decades. majority these failures are due unexpected toxicity — that is, safety issues revealed in trials were not apparent tests or lack efficacy. However, use more innovative tools, such as organs-on-chips, preclinical pipeline drug testing, tools able predict events prior clinical and so can be used this, well efficacy testing. Here, we review several disease areas, consider how models failed offer effective new treatments. We also make some suggestions human-relevant approach methodologies might applied address this.

Language: Английский

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The Evolution of Animal Models in Wound Healing Research: 1993–2017

Advances in Wound Care, Journal Year: 2019, Volume and Issue: 8(12), P. 692 - 702

Published: Oct. 24, 2019

Significance: Wound healing is a complex and dynamic series of events influenced by variety intrinsic extrinsic factors. Problematic wounds, particularly chronic wounds pathologic scars, remain clinically significant burdens. Modeling physiologic aberrant wound repair processes using in vitro or vivo models have contributed to Advances Care (AWC); however, the fidelity each model used, with respect its species-specific limitations, must be taken into account for extrapolation human patients. Twenty-five years published Repair Regeneration (1993-2017) AWC (2012-2017) were collected analyzed determine trends species utilization used. Recent Advances: In 25 years, 1,521 original research articles utilizing one more (total 1,665 models). Although 20 different used over course 5 most commonly utilized: human, mouse, rat, pig, rabbit. modeling was frequently, followed vitro, ex vivo, silico processes. Critical Issues: A comparison from 1993 1997 2013 2017 periods showed notable differences usage. Experiments mouse increased, while usage pig remained constant, rabbit rat declined recent time period examined compared two decades before. Future Directions: This analysis shows changes types which may attributed new knowledge, techniques, technology, and/or reagents. Explorations mechanisms limb regeneration noncutaneous tissues also shift time. Changes within journals (i.e., page expansion increased rejection rates), funding, expense influence observed shifts.

Language: Английский

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Oncolytic herpes virus G47Δ works synergistically with CTLA-4 inhibition via dynamic intratumoral immune modulation

Molecular Therapy — Oncolytics, Journal Year: 2021, Volume and Issue: 22, P. 129 - 142

Published: May 19, 2021

Oncolytic virus therapy can increase the immunogenicity of tumors and remodel immunosuppressive tumor microenvironment, leading to an increased antitumor response immune-checkpoint inhibitors. Here, we investigated therapeutic potential G47Δ, a third-generation oncolytic herpes simplex type 1, in combination with inhibitors using various syngeneic murine subcutaneous models. Intratumoral inoculations G47Δ systemic anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody administration caused enhanced activity when combined worked synergistically. Conversely, efficacy anti-programmed cell death protein-1 (PD-1) was equivalent that anti-PD-1 alone all models examined. The intratumoral anti-CTLA-4 shown recruit effector T cells into efficiently while decreasing regulatory cells. Furthermore, wide range gene signatures related inflammation, lymphoid lineage, activation highly upregulated therapy, suggesting conversion immune-insusceptible immune susceptible. effect proved specific long lasting. Immune subset depletion studies demonstrated CD4⁺ were required for synergistic curative activity. results depict dynamics modulation microenvironment provide clinical rationale checkpoint

Language: Английский

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New tools for immunologists: models of lymph node function from cells to tissues

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 10, 2023

The lymph node is a highly structured organ that mediates the body’s adaptive immune response to antigens and other foreign particles. Central its function distinct spatial assortment of lymphocytes stromal cells, as well chemokines drive signaling cascades which underpin responses. Investigations biology were historically explored in vivo animal models, using technologies breakthroughs their time such immunofluorescence with monoclonal antibodies, genetic reporters, two-photon imaging, and, more recently techniques. However, new approaches are needed enable tests cell behavior spatiotemporal dynamics under controlled experimental perturbation, particularly for human immunity. This review presents suite technologies, comprising vitro, ex silico developed study or components. We discuss use these tools model behaviors increasing order complexity, from motility, cell-cell interactions, organ-level functions vaccination. Next, we identify current challenges regarding sourcing culture, real measurements tool development analysis control engineered cultures. Finally, propose research directions offer our perspective on future this rapidly growing field. anticipate will be especially beneficial immunologists looking expand toolkit probing structure function.

Language: Английский

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Deciphering the Human Germinal Center: A Review of Models to Study T–B Cell Interactions

European Journal of Immunology, Journal Year: 2025, Volume and Issue: 55(2)

Published: Feb. 1, 2025

Interactions between T- and B cells in the germinal center reaction are instrumental for initiation, maintenance, downregulation of human adaptive immune response, leading to production antigen-specific antibodies long-lasting immunological memory. Replicating system remains challenging, with an over-reliance on animal models limited translational accuracy. There is increasing need new tools that accurately model function. This review evaluates existing 2D 3D vitro ex vivo their ability reproduce reaction, a particular focus B-cell interaction. We conclude although current able replicate certain features no completely complex GC process. outline challenges recreating fully functional suggest future directions research improve models, ultimately bringing us closer reproducing lymph node.

Language: Английский

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Tolerating Factor VIII: Recent Progress

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 10

Published: Jan. 10, 2020

Development of neutralizing antibodies against biotherapeutic agents administered to prevent or treat various clinical conditions is a longstanding and growing problem faced by patients, medical providers pharmaceutical companies. The hemophilia A community has deep experience with attempting manage such deleterious immune responses, as the lifesaving protein drug factor VIII (FVIII) been in use for decades. Hemophilia bleeding disorder caused genetic mutations that result absent dysfunctional FVIII. Prophylactic treatment consists regular intravenous FVIII infusions. Unfortunately, 1/4 1/3 patients develop anti-FVIII antibodies, referred clinically "inhibitors," which serious diathesis. Until recently, only therapeutic option these was "Immune Tolerance Induction," consisting intensive administration, extraordinarily expensive fails ~30% cases. There tremendous recent progress developing novel potential alternatives A, ranging from encouraging results gene therapy trials, other hemostatic (either promoting coagulation slowing down anti-coagulant fibrinolytic pathways) "bypass" need supplement replacement therapy. Although approaches are promising, there widespread agreement preventing reversing inhibitors remains high priority. Risk profiles therapies still unknown incomplete, will likely continue be considered optimal agent support surgery trauma, combine therapies. We describe here exciting studies, most pre-clinical, address immunogenicity suggest interventions reverse inhibitor development. Studies uptake, processing presentation on antigen-presenting cells, epitope mapping, roles complement, heme, von Willebrand factor, glycans, microbiome elucidating mechanisms primary secondary responses suggesting additional targets. Promising tolerogenic include development FVIII-Fc fusion proteins, nanoparticle-based therapies, oral tolerance, engineering regulatory cytotoxic T cells render them FVIII-specific. Importantly, studies highly applicable scenarios where establishing tolerance defined antigen

Language: Английский

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