Engineering and Delivering B Cells Using Biomaterials against Breast Cancer

Informations projet

END-BC

N° de convention de subvention: 101138825

DOI

10.3030/101138825

Projet clôturé

Date de signature de la CE 21 Decembre 2023

Date de début 1 Janvier 2024

Date de fin 30 Juin 2025

Financé au titre de

• European Research Council (ERC)

Coût total

Aucune donnée

Contribution de l’UE

€ 150 000,00

Coordonné par

UNIVERSITAETSKLINIKUM AACHEN
Germany

Periodic Reporting for period 1 - END-BC (Engineering and Delivering B Cells Using Biomaterials against Breast Cancer)

Période du rapport: 2024-01-01 au 2025-06-30

Résumé du contexte et des objectifs généraux du projet

Immunotherapy has revolutionized cancer treatment by harnessing the body’s own immune system to recognize and eliminate can cells. While remarkable clinical success has been achieved in certain hematological malignancies and some solid tumors, its effectiveness against breast cancer remains limited. Breast cancer continues to be one of the leading causes of cancer-related mortality worldwide, with approximately 30% of patients developing metastases despite advances in surgery, radiotherapy and drug therapy. Moreover, current therapeutic options are often associated with significant toxicity and high costs which significantly jeopardizes accessibility of the therapies, particularly in low- and middle-income countries where the burden of disease is rapidly increasing.

Adoptive cell therapy (ACT), including chimeric antigen receptor T cell (CAR-T) therapy, represents a powerful new modality capable of directly targeting and killing cancer cells. However, its clinical translation for solid tumors such as breast cancer has faced major challenges, including poor immune cell persistence and low infiltration of immune cells to tumor tissues, the immunosuppressive tumor microenvironment, complex and costly manufacturing processes, and safety concerns related to cytokine release syndromes. These limitations show the need for more effective and accessible immune cell-based therapies.

END-BC was proposed to address these challenges by developing a B cell-based ACT which is directly delivered via injectable hydrogels. Unlike conventional ACT approaches, B cells offer unique advantages, including intrinsic antigen-presenting capabilities, sustained antibody secretion, and potentially more scalable. By integrating biomaterial engineering, the project seeks to optimize B cell activation and delivery, thereby improving therapeutic efficacy while minimizing off-target effects. Ultimately, END-BC aims to explore the feasibility of developing an accessible, safe, and potent immunotherapies for breast cancer, and to lay the foundation for future clinical applications and for broader use of B cell-based therapies in oncology.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

1. Synthesis and optimization of a nanovesicle-based vaccine for B cell activation
A library of nanovesicle formulations was prepared by varying the composition and formulation parameters. Different formulation parameters were investigated to fine-tune the nanovesicles’ physico-chemical characteristics, including size distribution, surface chemistry and structural integrity, aiming to maximize B cell activation efficiency and reproducibility. The resulting optimized nanovesicles demonstrated superior stability, ensuring consistent performance in downstream B cell activation studies. This work established an essential and robust foundation for the use of nanovesicle-based vaccines in B cell activation.

2. Engineering of injectable hydrogels for B cell loading and release
A library of injectable hydrogels was developed through an integrated approach combining polymer chemistry, organic chemistry and physical chemistry. The material formulation was refined to allow rapid gelation under mild conditions that are compatible for cells, as well as to ensure high injectability and structural stability of the hydrogels. The time and manner of B cell addition during the hydrogel formulation were studied and optimized. The release and viability of B cell loaded in the hydrogels were studied in vitro. The hydrogel design improved cell viability of encapsulated B cells over extended periods, and release study demonstrates that B cells loaded in the hydrogels can be released. This platform enables controlled and sustained release of B cells, and offers a promising strategy for durable immune modulation with minimal invasion via fine needles.

3. In vivo proof of concept of B cell therapy in a tumor model
The feasibility and therapeutic potential of the B cell-based therapy were evaluated in vivo using a primary breast cancer model in mice. The study examined both the release of engineered B cells from the hydrogel after injection in vivo and their therapeutic efficacy. The results provided promising evidence that the hydrogel-based delivery system enables effective B cell delivery directly to tumor tissues, which could kill cancer cells. This proof-of-concept study validated the core biological premise of the END-BC project and confirmed the translational potential of the technology for treating breast cancer.

4. Intellectual property (IP) application and strengthening
Building on the scientific outcomes, a patent application was filed to protect the novel nanovesicle vaccine for B cell engineering. The IP portfolio was further strengthened through internal evaluation of patent claims, comparative freedom-to-operate analyses, and consultation with technology transfer experts. Two relevant technologies were generated and in preparation for IP protection, which are related to cell loading and release materials. These actions ensure that the key innovative elements of the platform are protected and can form the basis for future commercial partnerships and clinical translation efforts.

5. Translation feasibility and market research
A detailed analysis was conducted to assess the technical and commercial feasibility of advancing the B cell-based therapy toward clinical development. This included evaluation of scalability, manufacturing costs, regulatory pathways, and potential market positioning relative to existing cell and gene therapy products. Engagement with external advisors and industrial stakeholders provided valuable insights into the competitive landscape and potential routes for technology transfer. The outcomes of this work established a clear roadmap for the translation of the END-BC innovation from the laboratory toward preclinical and commercial development.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

A major technical achievement of the project was the development of injectable hydrogels with substantially improved mechanical properties and ease of use for in vivo applications. Through systematic optimization of the polymer composition and crosslinking conditions, the resulting materials exhibit rapid gelation, high injectability through fine needles, and robust stability once formed. These features overcome limitations of conventional hydrogel systems, which often require complex handling or invasive implantation. This advancement provides a versatile platform for minimally invasive delivery of immune cells and other biotherapeutics.
In parallel, the project optimized the hydrogel formulation to achieve superior performance in B cell loading and release. The refined composition of the hydrogel supports high cell viability and functional retention over extended periods. Controlled degradation and tailored mechanical properties enable sustained release kinetics and that B cells remain viable and active after injection. This represents a substantial improvement over existing delivery systems for immune cell therapies, which often compromise cell viability or provide insufficient control over cell release.