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

Project Information

GIPTRAP

Grant agreement ID: 101030158

DOI

10.3030/101030158

Project terminated on 25 May 2023

EC signature date 16 April 2021

Start date 1 January 2022

End date 31 December 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 160 932,48

EU contribution

€ 160 932,48

Coordinated by

BIOMEDAL SL
Spain

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

Reporting period: 2022-01-01 to 2023-12-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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