Biologicals targeting type 2 immunity: Lessons learned from asthma, chronic urticaria and atopic dermatitis

Abstract

During the last decades, progression of research has led to great achievements for treatment and therapy of several disabling disorders, particularly in the field of chronic inflammatory diseases. The increased knowledge of the molecular mechanisms operating in such diseases has represented the first step in this process, and the discovery of molecules able to interfere with the natural history of the diseases, has been the second. This review is focused on the effects of biologics on type 2 diseases such as asthma, chronic urticaria and atopic dermatitis, both biologics just approved for clinical application and also those that are currently undergoing clinical trials. We will also discuss aspects and emphasize clinical trials and recently published studies, as well as research that is currently in the progress, which will be highly relevant for basic immunologists. Likewise, we will cover aspects that are pertinent for clinical immunologists and highlight translational studies that are evaluating novel biologicals in animal models.Keywords: atopic dermatitis r bronchial asthma r chronic urticaria r precision medicine

Group 2 Innate Lymphoid Cells: A Double-Edged Sword in Cancer?

“…Preclinical studies have clearly shown that ILC2s promoted Th2-cell differentiation since, in their absence, Th2 response in mice is impaired when challenged with allergens or parasitic worms [15,54]. Accordingly, in humans, an increased number of ILC2s and activity were observed in patients with Th2-oriented disorders as respiratory allergy, atopic dermatitis, chronic rhinosinusitis and eosinophilic esophagitis [45,[54][55][56][57][58][59][60]. Notably, intrahepatic ILC2s contribute also to the process of fibrogenesis in liver diseases through secretion of AREG [61].…”

“…Indeed, it has been shown that ILC2s may exert APC activity for naïve CD4+ T cells since they express MHC-Class II and costimulatory molecule OX40L [45,58,64]. IL-4 has also trophic activity on basophils and mast cells (MC) which are short-lived circulating cells recruited to inflammatory sites (basophils) or long-lived tissue resident cells (MC) [45,47,55,59].…”

“…Such studies provide a rationale for therapeutically targeting both receptors, which is also to be considered complementary to other antitumor approaches. The anti-IL-4Rα mAb has recently been approved by regulatory agencies for the treatment of some allergic disorders as well as other mAbs targeting molecules/receptors of type 2 inflammation [59], which could show promising results at least in some tumors.…”

All the small things: How virus‐like particles and liposomes modulate allergic immune responses

“…This approach aims at the active induction of neutralizing autoantibodies against effector cytokines in allergic diseases. The active immunization approach follows a similar logic as passive immunization with biologics, which, in the recent years, has become an established treatment for severe cases of, e.g., allergic asthma by targeting effector molecules critically involved in the allergen‐specific immune response like IL‐4, IL‐5, or IL‐13 . However, compared to the high treatment costs and efforts (repeated injections) associated with passive immunization, active immunization against immune effector molecules might be advantageous, because it could represent a more cost‐effective therapy with the potential to induce a durable, long‐term, and polyclonal response against the targeted molecules.…”

Mepolizumab in Severe Eosinophilic Asthma: A 2-Year Follow-Up in Specialized Asthma Clinics in Greece: An Interim Analysis

“…The latest GINA recommendations suggest the use of mepolizumab as an add-on treatment for patients with severe eosinophilic asthma [2]. Mepolizumab is an IgG1/k class-humanized monoclonal antibody which blocks circulating interleukin-5 (IL-5) which is responsible for the development, maturation, and survival of eosinophils [3]. Several randomized controlled trials have shown the efficacy and safety of mepolizumab in patients with severe eosinophilic asthma [4][5][6]; however, to date, only a few studies have shown its effectiveness in a real-life setting [7][8][9].…”