Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell-based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell-based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell-based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.

Allergy Unit Hospital Regional Universitario de Málaga Instituto de Investigación Biomédica de Málaga ARADyAL Málaga Spain

Comparative Medicine The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna Medical University Vienna and University Vienna Vienna Austria

Department of Biochemistry and Molecular Biology School of Chemistry Complutense University of Madrid Madrid Spain

Department of Biomedical Sciences Dentistry and Morphological and Functional Imaging Respiratory Medicine Unit University of Messina Messina Italy

Department of Clinical Pharmacy and Pharmacology University Groningen University Medical Center Groningen and QPS NL Groningen Netherlands

Department of Immunology University Hospital Zurich University of Zurich Zurich Switzerland

Department of Medicine Section of Pharmacology University of Perugia Perugia Italy

Department of Medicine Surgery and Dentistry Scuola Medica Salernitana University of Salerno Salerno Italy

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Department of Respiratory Medicine and Allergology Institute for Clinical Science Skane University Hospital Lund Sweden

Department of Respiratory Medicine and Allergology Lung and Allergy research Allergy Asthma and COPD Competence Center Lund University Lund Sweden

Departments of Immunology and Dermatology Allergology University Medical Center Utrecht Utrecht The Netherlands

Experimental Studies Medicine at National Heart and Lung Institute Imperial College London and Royal Brompton and Harefield NHS Trust London UK

Faculty of Science Division of Pharmacology Department of Pharmaceutical Sciences Utrecht University Utrecht The Netherlands

Molecular Cell Biology Group National Heart and Lung Institute Imperial College London London UK

Pharmacology Unit Faculty of Medicine Institute for Drug Research The Hebrew University of Jerusalem Israel

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