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

Información del proyecto

GIPTRAP

Identificador del acuerdo de subvención: 101030158

DOI

10.3030/101030158

Proyecto finalizado el 25 Mayo 2023

Fecha de la firma de la CE 16 Abril 2021

Fecha de inicio 1 Enero 2022

Fecha de finalización 31 Diciembre 2023

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 160 932,48

Aportación de la UE

€ 160 932,48

Coordinado por

BIOMEDAL SL
Spain

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

Período documentado: 2022-01-01 hasta 2023-12-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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