Therapeutic potential of recombinant antibodies to neutralize immunogenic peptides in celiac disease

Informazioni relative al progetto

GIPTRAP

ID dell’accordo di sovvenzione: 101030158

DOI

10.3030/101030158

Progetto concluso il 25 Maggio 2023

Data della firma CE 16 Aprile 2021

Data di avvio 1 Gennaio 2022

Data di completamento 31 Dicembre 2023

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 160 932,48

Contributo UE

€ 160 932,48

Coordinato da

BIOMEDAL SL
Spain

Periodic Reporting for period 1 - GIPTRAP (Therapeutic potential of recombinant antibodies to neutralize immunogenic peptides in celiac disease)

Periodo di rendicontazione: 2022-01-01 al 2023-12-31

Sintesi del contesto e degli obiettivi generali del progetto

Celiac disease consists of an autoimmune response triggered by dietary gluten exposition in genetically predisposed individuals, around 1% of the population.
To this day, the only effective treatment is a permanent gluten free diet (GFD). However, a fully GFD is difficult to achieve, and symptoms persist in 65% of patients, with only 8% of them reaching duodenal-mucosa complete normalization.
In collaboration with international research institutions, Biomedal S.L. showed that at least two thirds of celiac patients consume gluten aware or unaware at least once per week, and only 11% do not ingest gluten in a period of four weeks.
GIPTRAP aimed at evaluating the potential use of antibodies against gluten immunogenic peptides (GIP) as therapeutic tools to reduce the effect of exposure to gluten in celiac disease patients.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

GIP neutralization capabilities of several antibodies were tested in vitro in an ELISA sandwich. Biomedal S.L. licensed G12 antibody showed the best results, reducing 97% of GIP signal. Neutralization still needs to be tested ex vivo to confirm that this GIP-capture does not induce celiac disease patient T-cells activity. An ethical committee has been obtained approving the protocol to purify T-cells from blood samples from healthy volunteers and celiac disease patients. Currently, samples are being collected and ex vivo assays will be carried out before the end of the year by Biomedal S.L. and collaborators.
Antibody G12 engineering has been carried out. Recombinant, Fab and scFv versions of G12 were generated and assessed for anti-GIP activity. The recombinant version was as efficient as the original. However, when Fab and scFv versions were used in an ELISA test, they were not as sensitive as G12. The scFv version will be used for antibody maturation by phage display before the end of the year by Biomedal S.L. and collaborators.
Antibodies have been produced using hybridoma cells, CHO and HEK mammalian cells, and E. coli bacterial cells, all in batch cultures. A hollow-fiber continuous culture system was acquired to enhance production yield. It will be used for matured antibody production, but still needs to be optimized.
In relation to project dissemination, Alicia participated in two life science student events at Universidad Pablo de Olavide to discuss career opportunities and promoted MSCA-IF-SE fellowships. She attended PEGS Europe 2022, a summit in Protein and Antibody Engineering, and Trasnfiere2023, a tech transfer trade fair organized in Malaga, Spain.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Alicia has also completed a training program that has equipped her with tools to follow and draft legal documents related to intellectual property, use R-Studio for multiple data analysis approaches, comprehend in vitro diagnosis and quality management regulation (ISO13485) and work within its framework, and improve her skills in project management and science communication. All this achieved in certified courses.
To sum up, accumulated results indicate that ex vivo antibody GIP-neutralization is feasible, especially if a matured antibody specifically design with this purpose is obtained. However, transferring this proof of concept into therapy will be a challenge in terms of production, delivery, clinical ethical clearance, and regulation. Still, tools and know-how produced during this project will help advancing celiac disease diagnostic and research.

Neutralization WP1