HEИндивидуална стипендия2023–2025

mAB · many(Anti)Bodies

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-12-01 → 2025-11-30
Финансиране от ЕС: 206 888 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Моноклоналните антитела се изследват чрез физически модели, за да се разбере как тяхната Y-образна форма и електрически заряд влияят върху вискозитета на разтвора. Това помага при създаването на лекарства с висока концентрация, които да могат да се инжектират подкожно.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

many(Anti)Bodies

Monoclonal antibodies are important medicines, but they are difficult to formulate at the high concentrations needed for subcutaneous self-injection. At these concentrations, antibody solutions can become too viscous, which limits practical use. A key feature of antibodies is that they are not simple spheres: they have a Y-shape, internal flexibility, and complex interactions that can be directional and strongly affected by electrostatics and solution properties. Small changes in pH or salt concentration can thus shift protonation of amino acids and therefore change how antibodies interact. The objective of the project was to build a predictive, physics-based framework that links (i) molecular features of antibodies to (ii) intermolecular interactions and solution structure, and finally to (iii) macroscopic behavior such as clustering and viscosity in crowded conditions. This requires multiscale coarse-grained models which are detailed enough to retain the essential physical ingredients, but simple enough to simulate many antibodies together over relevant length and time scales. A central motivation was that many commonly used descriptions treat electrostatics by means of a simplified, effective representation. This can be useful under certain conditions, but it may miss how heterogeneous surface charge patterns and ion rearrangements control real antibody–antibody interactions. The project therefore focused on resolving charge heterogeneity, testing different electrostatic treatments, and validating models against scattering and rheology experiments for a establishing a truly predictive and informative framework.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Many of the exceptional breakthroughs in pharmaceutics require the collective and interdisciplinary effort of the scientific community to overcome challenges and shortcomings involved in optimizing the formulation of the final product. Monoclonal antibodies, for instance, have been found to be highly effective for the treatment of various immunological and allergic diseases as well as for cancer treatments thanks to their high specificity. On the other hand, they typically present high viscosities in concentrated solutions, dramatically altering their flow properties. The direct consequence is the difficulty in preparing stable solutions suitable for subcutaneous self-administration which, compared to intravenous infusion, would be advantageous in terms of patient compliance and adherence to the treatment, and reduced healthcare costs. Currently, a univocal framework providing microscopic interpretation to the enhanced viscosity is missing. With my proposal many(Anti)Bodies, I aim to address this issue by putting forward an interdisciplinary approach which exploits soft matter and colloidal science to investigate the molecular origin of the observed macroscopic behavior in antibody solutions. By combining numerical simulations with experiments, I will first design an accurate single-molecule model that accounts for the anisotropic shape of the antibody and include all relevant ingredients that determine intermolecular interactions. Therefore, through advanced computational techniques, I will be able to bring the current understanding of the antibody collective behavior and rheological properties to a new level, by shedding light on their dynamics and self-association in crowded environments. With the direct collaboration of pharmaceutical industries, my proposal will ultimately guide the formulation of novel antibody-based biologics and inspire future studies where the features of the antibody are designed according to the desired solution properties.

Оригинален текст от CORDIS (на английски).

Участници

LUNDS UNIVERSITET · LundКоординаторШвеция