Department of Biomedicine

Background:

Allergen immunotherapy (AIT) is the cornerstone in the treatment of allergic children(Alvaro-Lozano et al., 2020). Until recently, the standard of care was avoiding the trigger, use of rescue medication and education to minimize the risk associated with accidental exposure.

With prevalence of food allergies rising, food allergen immunotherapy (F-AIT) is a promising alternative, but still with the limitation regarding different protocols (up-dosing steps, frequency of intake during maintenance, duration of maintenance), selection of allergen and patients, safety as well as long-term efficacy (de Silva et al., 2022). Different routes have been studied, including next to the oral route, also epicutaneous, sublingual, and subcutaneous routes (AS et al., 2019; Greenhawt et al., 2023; Kim et al., 2023).

Recently a trial proved that Omalizumab for 16 weeks was superior to placebo in increasing the reaction threshold for different food allergens (Wood et al., 2024).

Furthermore, a form of oral immunotherapy, the milk and egg ladder is increasingly used for IgE mediated cow’s milk and hen’s egg allergies, despite the lack of standardized protocols as well as recommendations regarding the selection of patients, prescription of rescue medication, availability of nutritionists or medical advice (Athanasopoulou, Deligianni, Dean, Dewey, & Venter, 2017; Hicks, Fleischer, & Venter, 2024; Hosaagrahara Ramakrishna et al., 2023; Vassilopoulou, McMilin, & Venter, 2023; Venter, Meyer, Ebisawa, Athanasopoulou, & Mack, 2022).

The FIND project has shown that F-AIT is practiced in various centres all over Europe with variation regarding inclusion/exclusion criteria as well as protocols (Rodriguez Del Rio et al., 2022). The results include a survey until February 2019, published in 2022. Since then, the availability of oral immunotherapy has broadened: Palforzia ® has been approved in 2020, as the first authorised oral treatment for persisting peanut allergy, new data have become available suggesting early start being more effective and therefore an update of the current data is needed.

We aim not only to repeat the survey but to include questions specifically regarding the cow’s milk and hen’s egg ladder.

EEACI Recommendations regarding for F-AIT and OIT protocols will be published in the coming months and will influence further the practice in Europe.

The questionnaire will be available in English only and will be hosted on a secure online platform, following European legislation in force.

Only one representative person of the same centre should reply to the questionnaire.

AIMS

Primary Objective:

-      To assess to which extent food immunotherapy, including food ladders, is being performed inside and outside clinical trials throughout Europe

Secondary Objective: 

-      To address how the treatment is being provided, especially in terms of setting, safety measures, protocols during maintenance phase, exit food challenges

-      To extend the database and network of centers across Europe for further use for the EAACI.

-      To identify geographical differences among the selected countries.

To identify weaknesses in the treatment implementation. 

Terminally ill patients often experience significant psychosocial distress having depressed mood, death anxiety, pain, and an overall poor quality of life. Recent evidence from pilot studies suggests that serotonergic psychedelics, including lysergic acid diethylamide (LSD) and psilocybin, produce significant and sustained reductions of depressive symptoms and anxiety, along with increases in quality of life and life meaning in patients suffering from life-threatening diseases. Additionally, serotonergic psychedelics may produce antinociceptive effects.

Personalized treatment in oncology requires predictive biomarkers and direct on-target drug response to tailor therapy regimens. However, many efforts to develop truly predictive biomarkers are limited due to only a handful of genetic aberrations demonstrating clear clinical benefit for ‘targeted’ treatments. Together with an emerging trend in using drug combinations rather than single compounds, large prospective clinical trials require long time and enormous investments to demonstrate only marginal benefits. In order to overcome these limitations hampering major breakthroughs, researchers have moved towards ex vivo screening or patient-derived xenograft models envisioning to provide clinically relevant data in a 4-week turnaround. Here we aim to combine single-cell transcriptomics with drug treatment on ex vivo spheroids in a prospectively collected and homogenous cohort of ascites samples derived from high-grade serous ovarian cancer patients to 1) define the cell composition of ascites, an abdominal fluid with malignant cells taken through regular drainage to release patients’ pain; 2) align patients outcome with molecular and cellular signatures and ex vivo drug response, 3) evaluate in silico predicted and cancer cell-specific drug response in patient-derived cultures, and 4) ultimately define novel non-genetic biomarker-drug axes improving personalized treatment. In detail, we will test currently applied and suggested drug regimens in real-time using a straightforward ex vivo spheroid culture system. With an already established single-cell RNA sequencing pipeline we will also identify individual patient tumor heterogeneity and evaluate in silico drug response ex vivo. Our ex vivo spheroid platform will test cell proliferation, apoptosis, and response to single drugs and combinations in ascites-derived samples. Our bimodal approach is novel and the consideration of tumor heterogeneity together with drug response in patients’ material has not been addressed. Thus, we believe that the setup described in this grant can be further developed into a clinical helpful predictive analysis scheme. Moreover, predictors and response patterns delivered by this proposal will be useful for their testing in future ovarian cancer clinical trials.