Bioengineering for Cell-based Therapies

Bridging bioprocess engineering and stem cell biology to accelerate the development of advanced cell therapies.

Cell Therapy

Bioengineering for Cell-based Therapies at iBET

At iBET, we employ our over 30 years of expertise to improve the manufacturing of cell therapy products for clinical applications.

Our interdisciplinary teams combine upstream and downstream bioprocess development technologies with state-of-the-art bioanalytical tools to support our partners at any stage of their cell therapy product development pipeline. Our approach privileges the intersection of process intensification, scalability, cost-effectiveness, and quality control to ensure potency of the final product.

 

Process design for cells as therapeutic products

In collaboration with academic and industrial partners, we focus on bioprocess development and intensification for scalable production of (stem-derived and immune) cell therapy products with improved potency.

We design scalable bioprocesses for autologous and allogeneic cells (human cells, including pluripotent stem cells, mesenchymal stem/stromal cells, CAR-T cells) and their derivatives (differentiated cells and extracellular vesicles, EVs), both at upstream and downstream levels.

We employ our expertise in single-cell and 3D culture strategies, bioreactor technology and rational development of downstream purification methods. Our efforts are directed towards the use of cGMP-compatible manufacturing platforms, based on disposable technology (bioreactors, perfusion systems and membrane chromatography tools) and on the use of xeno-free components (e.g. culture medium, matrices).

Expansion and differentiation of hPSC-derivatives for engineered tissues/organs

Ongoing R&D projects tackle the improvement of hPSC expansion and differentiation/maturation into functional cell types for the development of bioengineered tissues/organs for heart and liver regenerative medicine.

In collaboration with academic and industrial partners, we are developing biology-inspired protocols, combining the knowledge of cell/developmental biology with the expertise of bioprocess engineering, to generate hPSC-derived cardiac, liver and kidney cell types.

Key steps include the modulation of critical environmental factors, namely the metabolic substrate, dissolved oxygen, co-culture with other hiPSC-derivatives, biomaterials, and extracellular matrix (ECM) components.

Characterization and (cryo)preservation of cell therapy products

Our bioprocess development is integrated with robust bioanalytical tools, which support the monitoring of cell therapy products’ quality attributes. We employ “omics”-based bioanalytical tools and process analytical technologies (PAT), including Dielectric and Raman Spectroscopy, for improved process understanding and optimization. More traditional analytical assays are also applied whenever applicable.

We further develop (cryo)preservation protocols for human (stem) cells (adult, embryonic and induced pluripotent stem cells) to facilitate their storage and transportation. Strategies for the short- term (i.e. cold preservation) and long-term (i.e. cryopreservation and vitrification) of cells as single cells, 2D monolayers or 3D cultures are also available, using, for example, cell entrapment in a permeable hydrogel matrix.

Related Technologies

Cell Culture Approaches
Cell Culture Approaches
Bioreactor Platforms
Multi-Omics Tools
Metabolic Characterization
Imaging
Downstream Processing

Highlights

Development of a novel CAR-T therapy against pediatric leukemia
We joined a European consortium, led by OneChain Immunotherapeutics (OCI), and funded by the European Innovation Council (EIC) Transition Challenge (Grant Agreement nº 101113067), working to develop a promising CAR T-cell based therapy against T-cell acute lymphoblastic leukaemia.

We joined a European consortium, led by OneChain Immunotherapeutics (OCI), and funded by the European Innovation Council (EIC) Transition Challenge (Grant Agreement nº 101113067), working to develop a promising CAR T-cell based therapy against T-cell acute lymphoblastic leukaemia.

The novel therapy will use a subtype of T-cells (gamma delta), which are allogenic, eliminating donor dependency, and prone to scalable manufacture, therefore representing a promising off-the-shelf cell product. The carxall project (www.carxall.com) started in April 2023 and, in the next 3 years, the iBET team will be playing a key role in translating the production process to the industrial level.

EIC Transition Challenge
“Large-scale” production of hiPSC-derived cardiac cells in bioreactors
Within “BRAV∃” project and in collaboration with University of Navarra (UNAV, Spain) and University Medical Center Utrecht (UMCU, Netherlands), scalable bioprocesses for generation of cardiac cells derivatives (cardiomyocytes, cardiac fibroblasts, cardiac endothelial cells) from hPSC are being developed.

Within “BRAV∃” project and in collaboration with University of Navarra (UNAV, Spain) and University Medical Center Utrecht (UMCU, Netherlands), scalable bioprocesses for generation of cardiac cells (cardiomyocytes, cardiac fibroblasts, cardiac endothelial cells) from hPSC are being developed.

These cells are produced in stirred-tank bioreactors (up to 2L scale) and after comprehensive characterization of quality attributes, will be used to seed the BioVAD (Biological Ventricular Assisted Device) and will define the new functional cardiac tissue to be tested in large animal models. Know more: BravE (projectbrave.eu)

EU Horizon 2020
Enhanced bioprocess control to advance the manufacture of Extracellular Vesicles
In collaboration with University of Navarra (UNAV, Spain), we developed a scalable manufacturing workflow to maximize the production of extracellular vesicles (EV) from mesenchymal stem/stromal cells in stirred-tank bioreactors.

The integrated bioprocess increases EV production 5-fold compared to conventional methods, with optimal isolation using tangential flow filtration and size exclusion chromatography. We also explored the potential of Raman spectroscopy to continuously track metabolite levels in stirred-tank bioreactors, contributing to streamline the selection of optimal EV collection timepoints. Importantly, MSC-derived EV maintained their quality attributes and stimulated angiogenesis in vitro, therefore highlighting the therapeutic potential of EVs manufactured following a scalable and tightly controlled bioprocess. The work, developed under the scope of the CARDIOPATCH project, funded by Interreg-Sudoe, was selected as the cover feature for the special issue: “Advanced Cell Technologies” in Biotechnology and Bioengineering (Marta H Costa et al., 2023). 

Interreg-Sudoe
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Related Teams

Stem and Immune Cells Bioengineering Lab
Margarida Serra
Margarida Serra

Lab Head, Stem and Immune Cells Bioengineering Lab

Bridging engineering and stem cell biology to accelerate the development of advanced cell therapies.

Translational Immunology Lab
Nádia Duarte

Senior Scientist, Translational Immunology Lab

Strengthening immunology expertise at iBET, with a focus on developing tools and strategies to test and potentiate the effectiveness of advanced cell immunotherapies

Advanced Cell Models Lab
Catarina Brito
Catarina Brito

Lab Head, Advanced Cell Models Laboratory

Leveraging ATMP development with advanced human cell models

Downstream Process Development Lab
Cristina Peixoto

Head of Downstream Process Development lab, Coordinator of Bioproduction Unit

Ground-breaking technologies for purification of new modalities

Late-Stage R&D and Bioproduction Unit Team
António Roldão

Head of the Cell-based Vaccines Development Laboratory & Coordinator of Late-Stage R&D Unit

Late-stage R&D, scale-up and technology transfer for complex biopharmaceuticals production.

Mass Spectrometry Unit Team
Patrícia Gomes-Alves

Head of the Sanofi Satellite Lab | Coordinator of Analytical Services Unit and Mass Spectrometry Unit

Mass Spectrometry-based R&D services to support our partners in bioprocess understanding & development and in-depth characterization of biologics.

Publications

Bioengineering for Cell-based Therapies
2024
Bioengineering for Cell-based Therapies
2023
Bioengineering for Cell-based Therapies
2022
Bioengineering for Cell-based Therapies
2021
Bioengineering for Cell-based Therapies
2018
Bioengineering for Cell-based Therapies
2017
Bioengineering for Cell-based Therapies
2012