Search Results (22)

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance. Full article

Approximately 10–24% of people suffer from a cat allergy. Fel d 1, the major allergen, triggers reactions in approximately 94% of sensitized individuals. Current therapeutic strategies for allergic diseases primarily involve medication or immunotherapy to alleviate symptoms, which are often burdened by low efficacy, high cost, and extended duration, posing significant challenges for patients. In contrast, IgY antibodies offer a promising alternative by reducing the level of allergens produced by cats. In this study, T-cell epitopes of Fel d 1 were predicted using ProPred/CTLpred, connected via a suitable linker (GGGGS), and expressed in E. coli. Immunization of mice and hens with recombinant cFel d 1 yielded high-titer specific antibodies (IgG: 1:301,500; IgY: 1:4,194,304). Cats administered anti-cFel d 1 IgY-enriched yolk powder (1–3% of diet) for four weeks exhibited a 30–71% reduction in salivary Fel d 1. These findings indicate that the allergen epitope-targeted IgY strategy effectively reduces allergen levels in cats, providing a promising basis for preventing and treating allergic conditions. Full article

Food allergies (FA) are a major public health concern in both children and adults. Immunoglobulin E (IgE)-mediated FA is characterized by allergic reactions driven by allergen-specific IgE and the subsequent degranulation of mast cells and basophils. Current FA management primarily involves avoidance of allergen-containing food, and more recently, therapies such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and the anti-IgE biologic omalizumab. However, these interventions are not curative. The gut microbiome has been implicated in the development and regulation of oral tolerance to food antigens. This narrative review explores the role of probiotics, fecal microbiota transplantation (FMT), dietary interventions, and the interaction between the microbiome and OIT as potential strategies to manage established FA. We also explore barriers to their proliferation as part of regular clinical care. We conclude that future research should (1) address how the microbiome interacts with immunotherapies other than OIT, (2) explore the role of novel microbiome-based treatments like FMT as potential adjuvants to existing food allergy therapeutics, and (3) focus on developing standardized protocols and endpoints for microbiome-based therapeutics. Full article

Background/Objectives: Canine Diffuse Large B-cell Lymphoma (cDLBCL) is characterized by a high prevalence of MHC II DR (DLA-DR) antigen overexpression. Murine anti-pan-DLA-DR monoclonal antibodies (mAbs) B5 and E11 have been previously observed to promote death of cDLBCL cells in vitro and in vivo. Consequently, DLA-DR antigens are considered a prospective target for passive immunotherapy aside from CD20. While infusion of anti-pan MHC II mAbs has demonstrated tumor suppression in cDLBCL xenografted immunodeficient mice, the relative contributions of direct cellular versus immune-mediated mechanisms to this therapeutic effect remain undefined. This study aimed to dissect these potential mechanisms of mAb E11. Methods: Canine lymphoma and leukemia cell lines CLBL1 and CLB70 were incubated with full E11 antibody or its F(ab′)2 and Fab fragments and cell viability was assessed with sub-G1 assay then, NOD-SCID mice were xenotransplanted with 1.5 × 10⁷ canine CLBL1 cells expressing nanoluciferase and were infused either with mAb E11 or its fragments, each at 1 mg/kg body mass, twice weekly for three consecutive weeks. Tumor burden was monitored by assessing body weight, nanoluciferase activity in blood, and by flow cytometric analyses of bone marrow tumor cell content. Time to tumor progression (TTP) was calculated based on weight loss and luminescence measurements. Results: We observed cytotoxic activity of monovalent E11-Fab fragments in vitro and in vivo. The mean TTP for mice treated with irrelevant mouse IgG antibodies was 9.8 ± 4.65 days. In contrast, treatment with E11 Fab fragments resulted in a TTP of 19.1 ± 2.67 days, which was similar to that achieved with the full E11 mAb (19.5 ± 1.73 days) and E11 F(ab′)2 fragments (18.1 ± 2.9 days). Conclusions: Our findings demonstrate a potent antibody cytotoxicity mechanism that operates in vivo and is independent of cell surface MHC II crosslinking or Fc engagement. These data support the promising potential of E11-Fab fragments for further clinical development as a therapeutic agent in canine lymphoma. Full article

Background/Objectives: Oral immunotherapy with peanut protein powder is difficult to initiate in patients with a very low reactivity threshold to peanuts. For this specific group, an add-on treatment with omalizumab (anti-IgE monoclonal antibody) is helpful to tolerate the initial steps. Methods: After failed initiation in three children, an off-label approval from the individuals’ insurance was necessary for the premedication with anti-IgE ahead of a second approach at our center. Currently, the European countries have no approval from the European Medicines Agency (EMA) for the treatment of food allergies with omalizumab. Results: Under anti-IgE protection, our patients have restarted the oral immunotherapy without anaphylactic reactions and have reached the maintenance dose within the treatment protocol. Conclusions: For a few patients with initial anaphylactic reactions due to doses below the first treatment step (3 mg peanut protein powder), a premedication with omalizumab is not only safe but also reduces side effects, in particular anaphylactic reactions, and the time to reach the hundredfold higher maintenance dose (300 mg peanut protein powder). Full article

Food allergies result from dysregulated immune responses to dietary antigens. IgE antibodies are key in triggering allergic reactions through binding to high-affinity receptors on mast cells and triggering mast cell activation when crosslinked by allergens. In contrast, IgG antibodies—particularly IgG4—are linked to immunomodulation and tolerance. Allergen-specific memory B cells, especially IgG1+ cells, undergo class-switching to IgE, and IgE plasma cells underlie allergy persistence. Although there is no cure, allergen-specific immunotherapy (AIT) aims to achieve sustained unresponsiveness by gradually increasing allergen exposure. Oral immunotherapy (OIT), a form of AIT, induces a shift from a TH2-skewed response to a more regulated immune profile, characterized by a switch from IgE to IgG4 and IgA isotypes. This review outlines current insights into AIT’s cellular and humoral mechanisms, with implications for improving long-term outcomes and developing predictive biomarkers. Full article

Allergen immunotherapy (AIT) is a well-established treatment aimed at reducing allergen sensitivity by gradually exposing the immune system to increasing doses of allergens. This promotes desensitization and immune tolerance through multiple mechanisms. AIT offers long-term immune modulation and is considered a potentially curative certain forms of allergic diseases. Altered antibody responses is a key mechanism of AIT in the production of allergen-specific IgG4 antibodies, which act as blocking antibodies to prevent allergen binding to IgE on mast cells (MCs) and basophils. However, IgG4 responses are sometimes ineffective due to variations in antibody affinity and epitope targeting. Reverse class switching from IgE to IgG4 and selective depletion of IgE-producing B cells represent potential strategies to improve AIT efficacy. Tregs play a central role in AIT by suppressing Th2-driven allergic responses and promoting immune tolerance through anti-inflammatory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β. However, genetic and environmental factors may impair Treg function, leading to AIT failure. AIT reduces MC and basophil activation, leading to long-term suppression of allergic inflammation. It modulates IgE-FcεRI interactions and cytokine signaling pathways, but in some cases, anaphylactic reactions or resistance to MC desensitization may occur. Discussion and conclusions: While AIT is a highly effective allergy treatment, variability in immune responses can impact its success. Advances in biologic therapies offer potential synergies with AIT. Understanding these interactions will help refine AIT strategies and improve patient outcomes. Full article

The birch pollen allergen Bet v 1 is believed to be the main sensitizer among PR-10 allergens. Recent data have shown that some other PR-10 allergens also display sensitization activities, and Bet v 1-based immunotherapy is not effective for blocking allergic reactions to PR-10 proteins with low similarities to Bet v 1. Here, we investigated the sensitization potential of the major soybean allergen Gly m 4 and its cross-reactivity with Bet v 1. We demonstrated that Gly m 4 bound cholesterol and bile acids, including deoxycholic acid (DCA). Using qPCR, we showed that Gly m 4 induced the expression of genes encoding alarmins TSLP and IL-33 in intestinal-like Caco-2 cells; however, its fragments resulting from digestion by gastroduodenal enzymes or the DCA-bound Gly m 4 caused more pronounced gene upregulation. Using competitive ELISA, we demonstrated the low cross-reactivity of anti-Gly m 4 and anti-Bet v 1 IgG, raised in laboratory animals. Using mice allergy models with sensitization to birch or soybean allergens, we also showed a low cross-reactivity of Gly m 4- and Bet v 1-specific IgE, IgG1 and IgG2a. Thus, our findings support an assumption of the intrinsic sensitization capacity of Gly m 4 and the existence of Gly m 4-specific antibodies in sera of allergic patients. Full article

Background: Food allergies are a growing global health concern, particularly among children, with no widely approved curative treatment beyond strict allergen avoidance. Oral immunotherapy (OIT) has emerged as a promising strategy to induce desensitization, yet its implementation is limited due to high rates of allergic reactions and patient non-compliance. Omalizumab, a monoclonal anti-IgE antibody, has been proposed as an adjunct to OIT to enhance safety and efficacy. Objective: This systematic review and meta-analysis aim to evaluate the efficacy and safety of omalizumab in combination with OIT for IgE-mediated food allergy in children. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Cochrane Central databases to identify randomized controlled trials (RCTs), controlled clinical trials (CCTs), and observational studies assessing omalizumab as an adjunct to OIT in pediatric food allergy. Studies were evaluated for desensitization rates, immunological changes, adverse events, and quality-of-life improvements. Results: OIT combined with omalizumab led to significantly higher rates of desensitization, allowing patients to tolerate higher doses of allergens in a shorter timeframe compared to OIT alone. Omalizumab was associated with a reduction in adverse reactions, including anaphylaxis, and improved treatment adherence. However, the long-term sustainability of tolerance post-omalizumab discontinuation remains uncertain. Conclusions: Omalizumab facilitates rapid and effective desensitization in pediatric food allergy, enhancing the safety of OIT. Further research is needed to determine optimal treatment duration, long-term outcomes, and cost-effectiveness before widespread clinical adoption. Full article

Background: Sublingual immunotherapy (SLIT) has shown promise in mitigating allergic asthma symptoms; nevertheless, its high dose and prolonged duration of treatment raise safety concerns. This study explored the potential of Lactobacillus paracasei (L. paracasei) to enhance the effectiveness of SLIT in a mouse model of allergic asthma. Methods: Allergic asthma was induced in Balb/c mice following sensitization and challenge with a house dust mite (HDM) allergen. Subsequently, the mice were subjected to SLIT (66 and 132 µg) either alone or in combination with L. paracasei supplementation. Asthma-associated parameters, including rubbing frequency, IgE level, cytokine profiles, and histological changes, were evaluated to assess treatment efficacy. Results: mice that received SLIT 132 µg combined with the probiotic (combined 132) demonstrated a significant reduction in allergic symptoms (rubbing). This treatment strategy led to a marked IgE and eosinophil level decrease in serum; an increase in anti-inflammatory cytokines like IFN-γ and IL-10; and a reduction in pro-inflammatory cytokines IL-17 and TNF-α. The combination therapy also mitigated lung inflammation and supported the restoration of the structural integrity of the colon, promoting the recovery of goblet cells and mucus secretion. Probiotic treatment alone also effectively reduced IgE levels, increased IFN-γ, and decreased levels of IL-17 and TNF-α. Conclusions: The adjuvant effect of L. paracasei in enhancing SLIT represents a promising approach for improving asthma treatment efficacy. Full article

Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modification, specifically soaking and boiling (1–4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an “allergen ladder”. An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy. Full article

Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in Nicotiana benthamiana plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs’ pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine. Full article

Previous investigators have used various anti-HLA-F monoclonal antibodies (mAbs) to demonstrate that the tissue distribution of HLA-F is highly restricted. Notably, these mAbs differed in their immunodiagnostic capabilities. Specifically, mAbs Fpep1.1 and FG1 detected HLA-F intracellularly in B cells but not on the cell surface, whereas mAb 3D11 detected HLA-F on the cell surface. The presence of HLA-F on T cells was recognized by mAb FG1 but not by mAb Fpep1.1. mAb 3D11 detected HLA-F on the cell surface of activated B cells and on peripheral blood lymphocytes, but not on the normal cells. Importantly, mAb 3D11 revealed that HLA-F exists as a heavy chain (HC) monomer, rather than as an HC associated with B2m. Although these mAbs are believed to be specific to HLA-F, their monospecificity has not been formally established, which is critical for immunodiagnostic and therapeutic purposes. Previously, we investigated the diversity of HLA class I reactivities of anti-HLA-E mAbs using HLA-I coated multiplex bead assays on a Luminex platform. We reported that more than 80% of the HLA-E mAbs were cross-reactive with other HLA-I molecules, with exceptionally few truly HLA-E-monospecific mAbs. In the present investigation, we generated IgG mAbs against HCs of HLA-F in Balb/C mice and examined the cross-reactivity of anti-HLA-F mAbs with other HLA-I alleles using a multiplex bead assay on the Luminex platform. Beads coated with an array of HLA homo- and heterodimers of different HLA-Ia (HLA-A, HLA-B, and HLA-C) and Ib (HLA-E, HLA-F, and HLA-G) alleles were used to examine the binding of the anti-HLA-F mAbs. Only two mAbs were HLA-F monospecific, and five were HLA-Ib restricted. Several anti-HLA-F mAbs cross-reacted with HLA-E (n = 4), HLA-G (n = 3), HLA-Ia alleles (n = 9), HLA-G and HLA-Ia (n = 2), and HLA-Ib and HLA-Ia (n = 6). This monospecificity and polyreactivity were corroborated by the presence of HLA-F monospecific and HLA-I-shared sequences. This study emphasizes the need to monitor the mono-specificity of HLA-F for reliable immunodiagnostics and passive immunotherapy. Full article

(1) Background: Understanding how advanced cancers evade host innate and adaptive immune opponents has led to cancer immunotherapy. Among several immunotherapeutic strategies, the reversal of immunosuppression mediated by regulatory T cells in the tumor microenvironment (TME) using blockers of immune-checkpoint signaling in effector T cells is the most successful treatment measure. Furthermore, agonists of T cell costimulatory molecules (CD40, 4-1BB, OX40) play an additional anti-cancer role to that of checkpoint blocking in combined therapy and serve also as adjuvant/neoadjuvant/induction therapy to conventional cancer treatments, such as tumor resection and radio- and chemo- therapies. (2) Methods and Results: In this study, novel agonistic antibodies to the OX40/CD134 ectodomain (EcOX40), i.e., fully human bivalent single-chain variable fragments (HuscFvs) linked to IgG Fc (bivalent HuscFv-Fcγ fusion antibodies) were generated by using phage-display technology and genetic engineering. The HuscFvs in the fusion antibodies bound to the cysteine-rich domain-2 of the EcOX40, which is known to be involved in OX40-OX40L signaling for NF-κB activation in T cells. The fusion antibodies caused proliferation, and increased the survival and cytokine production of CD3-CD28-activated human T cells. They showed enhancement trends for other effector T cell activities like granzyme B production and lysis of ovarian cancer cells when added to the activated T cells. (3) Conclusions: The novel OX40 agonistic fusion antibodies should be further tested step-by-step toward their safe use as an adjunctive non-immunogenic cancer immunotherapeutic agent. Full article

Profilins are ubiquitous allergens with conserved structural elements. Exposure to profilins from different sources leads to IgE-cross-reactivity and the pollen–latex–food syndrome. Monoclonal antibodies (mAbs) that cross-react with plant profilins and block IgE-profilin interactions are relevant for diagnosis, epitope mapping, and specific immunotherapy. We generated IgGs mAbs, 1B4, and 2D10, against latex profilin (anti-rHev b 8) that inhibit the interaction of IgE and IgG4 antibodies from sera of latex- and maize-allergic patients by 90% and 40%, respectively. In this study, we evaluated 1B4 and 2D10 recognition towards different plant profilins, and mAbs recognition of rZea m 12 mutants by ELISAs. Interestingly, 2D10 highly recognized rArt v 4.0101 and rAmb a 8.0101, and to a lesser extent rBet v 2.0101, and rFra e 2.2, while 1B4 showed recognition for rPhl p 12.0101 and rAmb a 8.0101. We demonstrated that residue D130 at the α-helix 3 in profilins, which is part of the Hev b 8 IgE epitope, is essential for the 2D10 recognition. The structural analysis suggests that the profilins containing E130 (rPhl p 12.0101, rFra e 2.2, and rZea m 12.0105) show less binding with 2D10. The distribution of negative charges on the profilins’ surfaces at the α-helices 1 and 3 is relevant for the 2D10 recognition, and that may be relevant to explain profilins’ IgE cross-reactivity. Full article