Oral Immunotherapy Research Articles

Community and academic allergists’ perspectives on integrating biologics into food allergy care: A qualitative study

BackgroundBiologics are an important area of research and development, including for treatment of food allergy (FA). However, how allergists perceive the risks and benefits of biologics to treat FA remains largely unknown. ObjectiveTo explore how US-based allergists perceive the use of biologics in FA treatment. MethodsUsing a combination of purposive and snowball sampling, providers were recruited through direct solicitation by email to participate in a telephone or Zoom interview about their perceptions of the risks and benefits of current and future FA treatment options. Interviews were transcribed, deidentified, and coded to conduct a thematic analysis. ResultsWe conducted 60 interviews with providers from 34 states working either in community practice (53.3%) or academic medical centers (46.7%). Our sample was primarily non-Hispanic White (60.0%) and men (56.7%). The plurality was in their 40s (41.7%). Our findings clustered in the following 4 main themes: (1) perceived benefits of biologics, (2) ideal use of biologics, (3) concerns about biologics, and (4) biologics as the perceived future of FA. Community and academic providers had largely similar views, but academic providers more often emphasized the benefits of biologics, and community providers were, on the whole, more supportive of using biologics as an adjunct to oral immunotherapy rather than as monotherapy. ConclusionThis study indicates that providers hold mixed views about the use of biologics to treat FA. However, most were enthusiastic about prescribing biologics for FA while also being highly concerned about the cost to patients and the health care system.

Home multifood oral immunotherapy microdosing with Dartmouth Spoon Sheets

Home multifood oral immunotherapy microdosing with Dartmouth Spoon Sheets

Baked Egg Oral Immunotherapy: Current State in Pediatric Age.

Hen's egg allergy is one of the most common food allergies in the Western world, with an increase in recent years. It affects about 9.5% of the pediatric population, and the onset most often occurs before the first year of life. The occurrence of spontaneous oral tolerance acquisition varies among studies, but it is generally high by school age. Nowadays, allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of hen's egg allergy. Specifically, many children with hen's egg allergy may tolerate baked eggs. Food processing, specifically high temperatures, alters the allergenicity of hen's egg proteins by causing conformational changes in allergen epitopes, which makes them less allergenic. This review aims to discuss the scientific evidence in the field of baked egg oral immunotherapy in hen's egg-allergic children, with a meticulous examination of the pertinent literature surrounding the subject matter.

HLA-DR+ regulatory T cells and IL-10 are associated with success or failure of desensitization outcomes.

Omalizumab (XOLAIR®)-assisted multi-food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab-assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab-assisted mOIT and desensitization outcomes has not yet been fully elucidated. In this study, due to the key roles of regulatory T (Treg) cells and the type 2 helper T cell (Th2) pathway in immune tolerance to food allergens, we aimed to characterize their association with the desensitization outcomes of omalizumab-assisted mOIT. Mass cytometry and multiplex cytokine assays were performed on blood samples obtained from participants with allergies to peanut, cashew, or milk in our phase 2 clinical study (NCT02626611). Comprehensive statistical and bioinformatic analyses were conducted on high-dimensional cytometry-based single-cell data and high-throughput multiplex cytokine data. Our results demonstrated that the frequency of HLA-DR+ Treg cells, and the production of Th2 cytokines (IL-4, IL-5, IL-13, and IL-9) as well as the immunoregulatory cytokine IL-10 by peripheral blood mononuclear cells (PBMCs) was significantly increased in cultures with allergen compared to cultures with media alone at baseline (Week 0). We also observed increased frequency of allergen responsive HLA-DR+ Treg cells and enhanced production of IL-10 by PBMCs in participants who achieved successful desensitization compared to those with failure of desensitization. However, the production of Th2 cytokines by PBMCs did not show significant differences between participants with different desensitization outcomes (success vs. failure of desensitization), despite omalizumab-assisted mOIT inducing a significant reduction in the production of Th2 cytokines. We demonstrated that the frequency of HLA-DR+ Treg cells and IL-10 cytokine production by PBMCs are associated with desensitization outcomes of omalizumab-assisted mOIT. These findings suggest potential immunological parameters that could be targeted to enhance desensitization success rates.

Allergen immunotherapy and eosinophilic esophagitis: friends or foes?

The connection between eosinophilic esophagitis (EoE) and food and airborne allergens is complex. Exposure to allergens (mainly food) is often the trigger for EoE flares. The development of EoE has been described as a side effect of allergen immunotherapy, especially oral immunotherapy (OIT, with food allergens), while isolated cases of EoE have been reported during sublingual immunotherapy (SLIT, with extracts of aeroallergens). EoE is currently recognized as a common side effect of OIT, while a solid correlation between SLIT and EoE is missing. Animal models have been developed to study the pathophysiological link between sensitization to aeroallergens and the induction of EoE and will probably provide an interpretation of why there are cases of EoE developed during SLIT. Recent findings in animal models suggest a genetic connection to EoE development after sensitization and re-exposure to airborne allergens. Subcutaneous allergen immunotherapy does not have a causative effect on EoE; on the contrary, a beneficial effect on EoE has been reported. Moreover, epicutaneous immunotherapy with a vector containing milk has also been used to treat children with milk-induced EoE. Discovering the immune links between allergens and EoE will further guide the proper use of allergen immunotherapy and help define future strategies for the management of EoE.

Multi-Functional AIE Phototheranostic Agent Enhancing αPD-L1 Response for Oral Squamous Cell Carcinoma Immunotherapy.

Oral squamous cell carcinoma (OSCC) represents a prevalent head and neck malignancy with surgical intervention as the primary clinical option. Immunotherapy, particularly immune checkpoint blockade (ICB) targeting PD-1/PD-L1 shows great promise but is impeded by the immunosuppressive tumor microenvironment and low PD-L1 expression in OSCC. Herein, the "all-in-one" phototherapeutic nanoparticles (TSD NPs) are reported with balanced reactive oxygen species and photothermal conversion capacity for combined photoimmunotherapy and ICB immunotherapy against OSCC. A novel electron acceptor, 3-(dicyanomethylene)-2,3-dihydrobenzothiophene-1,1-dioxide (DTM), is introduced to develop the phototherapeutic agent with aggregation-induced emission (AIE) feature and NIR-II fluorescence centered at 1000nm. Benefiting from the AIE feature and the DTM acceptor, the resultant TSD NPs also exhibit strong type I reactive oxygen species (ROS) generation and high photothermal conversion efficiency (45.3%), which can profoundly induce immunogenic cell death (ICD), activate cytotoxic T lymphocytes, and convert the immunosuppressive tumor microenvironment into an immune-supportive one. Additionally, TSD NPs upregulate the PD-L1 expression on OSCC cells, thus enhancing the efficacy of combined treatment with αPD-L1 ICB immunotherapy. This results show that the synergistic treatment of TSD NPs and αPD-L1 effectively eradicates solid OSCC tumors without adverse effects on normal tissues, proving a novel and promising strategy for OSCC management.

Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral Immunotherapy in Infants and Toddlers in a Real-World Setting

Oral immunotherapy (OIT) for food allergy has been largely studied in older children within the context of clinical trials, and its availability has historically been limited for younger patients with food allergy. Data has shown that the most impact may actually be seen with the use of OIT in younger infants and toddlers. To evaluate the safety and feasibility of OIT in subjects younger than 24 months in a real-world setting using commercially available food products. This was a retrospective study of subjects 24 months and younger initiated on OIT for peanut, tree nut, or sesame allergy within the Scripps Clinic allergy department. Medical records were reviewed for data regarding initial oral food challenges (OFCs), OIT, and adverse outcomes. Fifty-two subjects under 24 months of age were initiated on OIT. Most subjects (84.6%) were on single food OIT, some (15.4%) were on multi-food OIT. No increased adverse outcomes were observed on multi-food OIT. Of the 59 initial OFCs, objective reactions occurred during 42 challenges, the majority being low grade reactions. During initial OFCs, 86.1% of peanut allergic children tolerated 1/8 of one Bamba stick with no reaction. The majority (73.1%) of subjects up-dosed at home and most (51.9%) had no reactions while up-dosing. Some had low grade cutaneous reactions, none requiring epinephrine or emergency evaluation. OIT in infants is safe and feasible to perform in a real-world setting using commercially available food products with at home up-dosing, thus increasing the availability of OIT for patients.

Omalizumab Implementation in Practice: Lessons Learned From the OUtMATCH Study

In February 2024, omalizumab was approved by the Food and Drug Administration for the treatment of food allergy, based on data from the landmark Phase 3 clinical trial “Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH).” In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary endpoints, demonstrating a large effect size in multi-allergen desensitization compared to placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. . Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or co-treatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes.

Improving Adherence Through Collaboration and Care Coordination in the Management of Food Allergies and Asthma

Food allergies and asthma significantly impact individual health and global healthcare systems. Despite established management protocols for asthma and the emerging use of oral immunotherapy for food allergy, adherence to treatments remains a challenge for healthcare professionals and patients. This review explores the differences in adherence required of asthma and food allergy treatments and strategies to improve adherence. We highlight the role of collaborative care coordination among healthcare professionals in enhancing adherence in asthma and food allergy management and improving patient outcomes.

Peanut allergen characterization and allergenicity throughout development.

Peanut allergy (PA) in children is a major concern. There is a need for better biological material for both diagnosis and oral immunotherapy (OIT) treatments. The unique state of seeds at early reproductive stages may affect the allergenicity of storage proteins, and impact clinical diagnostic and OIT protocols. The objective of this study was to evaluate the major allergen content in sequential seed developmental stages and monitor allergenicity via specific IgE binding quantification and skin prick testing. Seeds were collected from peanut plants and sorted into five developmental stages: initial (S1), developing (S2), full-size without coloration (S3), full-size with coloration (S4), and fully mature (S5) seeds. Samples were characterized by RNA-Seq, ELISA, and immunohistochemistry. Lyophilized, ground preparations were used for evaluation of skin test responses in sixty challenge-proven PA children. Gene expression, protein content, and specific IgE binding of allergenic proteins increased throughout seed maturation and development. An expression bias towards the less allergenic A-genome copy of the major allergen Ara h 2 was found in earlier stages, especially in stage S2. Immunohistochemical staining showed that Ara h 2 is more dispersed in the cell and less accumulated within organized bodies at stage S2 versus stage S4. Significant differences were found in mean wheal responses between the commercial peanut extract (equivalent to stage S5) and stages S1 and S2, but not with stage S4, upon skin prick testing in subjects with PA. The observed decrease in peanut-specific IgE binding of immature peanut seeds may be a result not only of decreased amounts of allergenic proteins, but also of profound changes in seed composition and conformation. This may be significant for developing a safer and more effective peanut OIT protocol.

Monitoring for eosinophilic esophagitis in food oral immunotherapy.

Monitoring for eosinophilic esophagitis in food oral immunotherapy.

Cost trends of metastatic renal cell carcinoma therapy: the impact of oral anticancer agents and immunotherapy.

Immunotherapy (IO) and oral anticancer agents (OAA) have improved outcomes for metastatic renal cell carcinoma (mRCC), but there is a need to understand real-world costs from the perspective of payers and patients. We used retrospective fee-for-service Medicare 100% claims data to study patients diagnosed with mRCC in 2015-2019. We identified initial treatment type and costs (the year after diagnosis) and analyzed differences in monthly and 12-month costs over time and between OAA, IO, and combination groups and the association between Out-Of-Pocket (OOP) costs and adherence. We identified 15 407 patients with mRCC (61% male; 85% non-Hispanic White). A total of 6196 received OAA, IO, or combination OAA/IO as initial treatment. OAA use decreased (from 31% to 11%) with a simultaneous rise in patients receiving IO (3% to 26%) or combination IO/OAA therapy (1% to 11%). Medicare payments for all patients with mRCC increased by 41%, from $60 320 (95%confidence interval = 58 260 to 62 380) in 2015 to $85 130 (95% confidence interval = 82 630 to 87 630) in 2019. Payments increased in patients who received OAA, IO, or combination OAA/IO but were stable in those with other/no treatment. Initial higher OOP responsibility ($200-$1000) was associated with 13% decrease in percent days covered in patients receiving OAA in the first 90 days of treatment, compared with those whose OOP responsibility was less than $200. From 2015 to 2019, costs for Medicare patients with mRCC rose substantially due to more patients receiving IO or IO/OAA combined therapy and increases in costs among those receiving those therapies. Increased OOP costs was associated with decreased adherence.

Salivary Microbiome Relates to Neoadjuvant Immunotherapy Response in OSCC

Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of Eubacterium infirmum, Actinobaculum, and Selenomas (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4+, CD14+, CD68+, and FOXP3+ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.

Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study.

Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.

Differences in familiarity with oral immunotherapy among caregivers of White and Black children with food allergy

BackgroundPotential racial and ethnic disparities related to oral immunotherapy (OIT) have not been fully described among children with food allergy (FA). ObjectiveTo characterize the differences in attitudes toward, familiarity with, and utilization of OIT among non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic or Latino (H/L) caregivers of children with FA. MethodsSurveys were administered to the caregivers of children enrolled in Food Allergy Outcomes Related to White and African American Racial Differences, a prospective, multisite cohort of children with FA. The distribution of responses by caregiver-reported race and ethnicity was described using an analysis of variance for continuous outcomes and χ2 tests for categorical outcomes. A logistic regression model was used to determine associations between familiarity with OIT as a treatment option and various other covariates. ResultsThe NHB and H/L respondents were more frequently not familiar with OIT compared with NHW responders (54.3% and 62.5% vs 9.2%, P < .001). This finding remained true, even after adjusting for household income (odds ratio: 0.1, 95% CI: 0.1-0.4 for NHB participants and odds ratio: 0.1, 95% CI: 0.0-0.3 for H/L participants). NHB and H/L participants more frequently reported that they had never heard of OIT before the survey compared with NHW participants (76.7% and 50.0% vs 26.7%, P < .001). None of the NHB and H/L respondents initiated OIT compared with 14.8% of NHW participants (P < .001). ConclusionIn the Food Allergy Outcomes Related to White and African American Racial Differences cohort, familiarity with OIT was lower among caregivers of minoritized racial and ethnic groups, even after adjusting for household income.

Efficacy and safety of low-dose sesame oral immunotherapy in paediatric patients: a protocol for a single-centre, randomised controlled trial

IntroductionSesame allergy, though with low prevalence, can result in severe, potentially life-threatening reactions and poses challenges in allergen avoidance due to hidden sources. In the majority of patients, sesame allergy...

Novel Effective Therapeutic Regimen for Recurrent/Metastatic Head and Neck Squamous Cell Cancer: Concurrent Triple Oral Metronomic Chemotherapy and Immunotherapy.

Novel Effective Therapeutic Regimen for Recurrent/Metastatic Head and Neck Squamous Cell Cancer: Concurrent Triple Oral Metronomic Chemotherapy and Immunotherapy.

The use of boiled peanut oral immunotherapy in children

The use of boiled peanut oral immunotherapy in children

Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy.

Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy.

Insights into the clinical, immunologic, and genetic underpinnings of food allergy.

The last few decades have seen striking changes in the field of food allergy. The prevalence of the disease has risen dramatically in many parts of the globe, and management of the condition has undergone major revision. While delayed introduction of common allergenic foods during infancy was advised for many years, the learning early about peanut allergy (LEAP) trial and other studies led to a major shift in infant feeding practices, with deliberate early introduction of these foods now recommended. Additionally, the Food and Drug Administration approved the first treatment for food allergy in 2020-a peanut oral immunotherapy (OIT) product that likely represents just the beginning of new immunotherapy-based and other treatments for food allergy. Our knowledge of the environmental and genetic factors contributing to the pathogenesis of food allergy has also undergone transformational advances. Here, we will discuss our efforts to improve the clinical care of patients with food allergy and our understanding of the immunological mechanisms contributing to this common disease.