On the mark: genetically engineered immunotherapies for autoimmunity.

On the mark: genetically engineered immunotherapies for autoimmunity. Curr Opin Immunol. 2019 Sep 26;61:69-73 Authors: Ellebrecht CT, Lundgren DK, Payne AS Abstract Current therapies for autoimmunity cause significant morbidity and mortality. Adoptive immunotherapy using genetically engineered T cells has led to durable remissions of B cell leukemias and lymphomas, raising the question of whether the approach can be modified to target autoreactive B and T cells to induce durable remissions of autoimmunity. Here we review antigen-specific approaches to modify immune cells to treat autoimmune disease. We focus on recent studies that aim to eliminate or suppress autoimmunity by targeting the disease-causing B or T cells through their B cell receptor or T cell receptor specificities. PMID: 31563849 [PubMed - as supplied by publisher]
Source: Current Opinion in Immunology - Category: Allergy & Immunology Authors: Tags: Curr Opin Immunol Source Type: research

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Conclusions The clinical trials discussed here, which include several trials investigating novel therapeutic targets, demonstrate that translational research in pemphigus and pemphigoid is a fast-growing field. We thus expect that several novel treatments will be shortly available for the treatment of pemphigus and pemphigoid patients. Given the high, and thus far unmet, medical need in this field (110), this is highly encouraging and will hopefully improve the quality of life of the affected patients. In addition to the compounds and targets described here, several new targets have been recently identified in preclinical...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Hiromi Kubagawa1*, Kazuhito Honjo2, Naganari Ohkura3, Shimon Sakaguchi3, Andreas Radbruch1, Fritz Melchers1* and Peter K. Jani1* 1Deutsches Rheuma-Forschungszentrum, Berlin, Germany2Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States3Immunology Frontier Research Center, Osaka University, Osaka, Japan It is now evident from studies of mice unable to secrete IgM that both non-immune “natural” and antigen-induced “immune” IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since iden...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Hui Zhou, Xiaoyan Fu, Qian Li and Ting Niu* Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clin...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Roser Calvo* Patient Safety, Safety Science, AstraZeneca Pharmaceuticals, Gaithersburg, MD, United States Immune-related hematological adverse events are amongst the rare but potentially life-threatening complications of immune checkpoint inhibitors. The spectrum of these toxicities is broadening as the number of patients exposed to these agents is increasing. Yet, they are still relatively unknown to many clinicians, possibly due to a lack of specific diagnostic criteria, which poses a challenge for their recognition and proper reporting, and partly due to their low incidence, often too low to be noted in most c...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Tabea Haug1, Michael Aigner1, Moritz M. Peuser1, Carolin D. Strobl1, Kai Hildner2, Dimitrios Mougiakakos1, Heiko Bruns1, Andreas Mackensen1 and Simon Völkl1* 1Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany 2Department of Internal Medicine 1, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany The recently discovered population of TCRαβ+ CD4–/CD8– (double-negative, DN) T-cells are highly potent suppressor cells in mice and humans. In preclinical transplantation m...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion and Perspectives Being exquisitely regulated by “writers,” “erasers,” and “readers,” additional repelled proteins or miRNAs, m6A modification relates to nearly any step of mRNA metabolism, as well as ncRNA processing and circRNA translation. There is compelling evidence suggesting that m6A modification is especially critical in a variety of pathologic and physiologic immune responses including T cell homeostasis and differentiation, inflammation, and type I interferon production. Further results have indicated that aberrancies of interferon and Th17 frequencies in systemic lu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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