Webinar CAR Therapy Today & Tomorrow

Webinar CAR Therapy Today & Tomorrow

CAR Therapy: Today & Tomorrow

Explore available CAR therapies, differentiation, development challenges, and lessons learned.

Key areas of focus include:

Would you like to familiarise yourself with CAR Therapies? Watch the replay to explore CAR-based Cell Therapy with our scientist, Somayeh Rezaeifard, elaborating on the various available CAR therapies, their differentiation, current challenges in therapy development, and lessons learned until today.

Whether you’re part of an academic research group, pioneering a new biotech, or working at a global CGT leader, this webinar brings together various aspects of CAR therapies to explore, discuss, and learn.

Key Learnings

  • Comprehensive overview of various CAR therapies
  • Breaking Down CAR Structure with comparison among CAR T, macrophages, and NK frameworks
  • Current CAR T status limitations in development and application
  • Critical factors that influence the quality of CAR therapy products
  • Lessons learned to guide new CAR-based therapy development

Join the conversation and equip yourself with the latest knowledge and insights in CAR-based immunotherapy.

iPSC Reprogramming & Transdifferentiation

iPSC Reprogramming & Transdifferentiation

Unlocking Cellular Potential With iPSC Reprogramming and Cell Transdifferentiation

iPSC reprogramming and transdifferentiation both offer exciting opportunities in cell biology. Learn how these approaches are revolutionizing regenerative medicine and cell therapy.

What is Cellular Reprogramming?

Cellular reprogramming is a process by which an adult, specialized somatic cell is transformed into a pluripotent state—an iPSC (induced pluripotent stem cell). These stem cells can differentiate into any cell in the body. 

As such, cellular reprogramming presents new opportunities in personalized medicine, disease modelling, and tissue regeneration and represents a monumental step towards a future in which we can alter cellular identities to combat diseases and enhance human health.

What Are Induced Pluripotent Stem Cells (iPSCs)?

iPSCs are stem cells reprogrammed from fully differentiated cells, such as skin or blood cells. While the ability of hiPSCs to differentiate into virtually any cell type is a fundamental characteristic, it’s important to distinguish this from the actual process of hiPSC reprogramming. Reprogramming refers to the initial conversion of differentiated adult cells into pluripotent stem cells. The differentiation of these reprogrammed cells into various cell types, similar to what embryonic stem cells can do, is a separate phase that follows the reprogramming. This distinction is crucial for understanding the scope and potential applications of hiPSC technology in research and clinical settings.

The Advantages & Limitations of iPSCs

iPSCs have generated interest in stem cell research for several reasons:

Origin from Patient-Specific Cells: hiPSCs can be derived from an individual’s cells, reducing the risk of immune rejection when used for transplantation.

Disease Modelling: Researchers can create hiPSCs from patients with genetic disorders or diseases and study disease mechanisms at the cellular level to screen potential drug candidates.

Regenerative Medicine: By differentiating into tissue/organ-specific cell types, hiPSCs hold the potential to replace damaged or malfunctioning tissues and organs, providing tailored solutions for patients.

Ethical Advantages: iPSCs circumvent some ethical concerns associated with embryonic stem cells, as they do not require the destruction of embryos for their generation.

While iPSCs offer numerous advantages in stem cell research and regenerative medicine, they also come with certain disadvantages and challenges that need to be addressed.

Tumorigenic potential: Tumorigenic potential in iPSCs is linked to genetic and epigenetic memory and differentiation efficiency. Incomplete differentiation, where some cells remain undifferentiated, increases the risk of tumour formation. To mitigate these risks in iPSC-based therapiesit’s crucial to ensure complete and efficient differentiation.

Genetic & Epigenetic Variability: Although we already discussed genetic and epigenetic modifications previously, it’s important to clarify that such changes can arise during the reprogramming process, during subsequent cell culture, or even pre-existing in the donor somatic cells. Each source contributes uniquely to the variability observed in iPSCs, impacting their behaviour and differentiation capacity.

Inefficiency & Variability: Generating iPSCs can be inefficient, with a relatively low success rate in some cases.

Immunogenicity: While hiPSCs generated from a patient’s cells can reduce the risk of immune rejection, there may still be immune responses against hiPSC-derived cells sometimes induced for ex-vivo cell culture

Time & Cost-Intensive: The generation and characterization of iPSCs are time-consuming and costly processes.

Ethical Considerations: Although reprogrammed cells are an ethical alternative to embryonic stem cells, there are still ethical considerations related to their use, specifically involving manipulating human genetic material.

iPSC Reprogramming Techniques

Viral Vector-based: Viral vector-based reprogramming can involve various types of viruses. While lentiviruses and retroviruses can integrate reprogramming factors into the host cell’s genome, raising concerns about genomic integration and tumorigenicity, adenoviruses are also used in reprogramming. Importantly, adenoviruses do not integrate their genetic material into the host genome, potentially reducing these risks.

mRNA-based: mRNA-based reprogramming uses synthetic messenger RNA (mRNA) to deliver reprogramming factors in a non-integrative manner, which is safer in terms of avoiding genome alteration. Although this method typically involves transfection, mRNA can be introduced into cells through other techniques, broadening its application. However, it is generally considered less efficient than viral methods.

Protein-based: Direct delivery of reprogramming factors as proteins overcome genomic integration concerns, but it may require optimization to enhance reprogramming efficiency.

Small Molecule-based: Small Molecule-based reprogramming involves using small molecules that can mimic the functions of reprogramming factors, offering an alternative strategy to induce pluripotency. While this approach is less well-established than other methods, it reduces complexity. However, it’s important to note that these small molecules can induce reorganization of the host genome, which may have safety implications.

The choice of delivery method depends on the specific goals of the research or clinical application, and factors such as efficiency, safety, and potential genomic alterations must be considered.

What is Transdifferentiation?

In contrast to iPSC reprogramming, which involves reverting a specialized cell type to a pluripotent state before differentiating it into another type, transdifferentiation consists of redirecting one specialized cell type directly into another, bypassing the pluripotent stage entirely.

Transdifferentiation is initiated by a combination of changes in gene expression patterns, including specific transcription factors, signalling pathways, and epigenetic modifications. These factors work together to redirect a specialized cell type into another without reverting to a pluripotent state.

The Key Differences Between iPSC Reprogramming and Transdifferentiation

iPSC reprogramming and transdifferentiation are two distinct approaches in cellular biology, each with notable differences. As summarised in this image in Nature, these methods alter cell states, specifically geared towards applications in regenerative medicine and cellular therapy.

iPSC reprogramming involves converting a differentiated (adult) cell, such as a skin cell, into a pluripotent stem cell. 

Transdifferentiation, or direct reprogramming, takes a different approach. It involves converting one type of adult cell directly into another without the need for a pluripotent stage.

Recognizing Challenges & Future Prospects

Both iPSC reprogramming and transdifferentiation methodologies have made remarkable progress in a short amount of time, but still face challenges. The current limitations of iPSCs and transdifferentiation include the risk of tumorigenicity, genetic and epigenetic variability, and the need for further optimization to enhance efficiency. 

Future prospects for iPSC reprogramming and transdifferentiation are promising due to ongoing advancements in understanding the underlying molecular mechanisms and improving the technologies. Researchers are continually developing safer and more efficient methods, which could lead to breakthroughs in personalized medicine, disease modeling, and regenerative therapies. As these techniques become more refined, their potential to transform medical treatments and outcomes becomes increasingly feasible.

The integration of emerging technologies and innovative approaches will undoubtedly continue to shape the future of these transformative fields.

Conclusion

The remarkable ability to alter a cell’s identity through induced reprogramming and transdifferentiation has ushered in a new era of science.

However, it must also recognize the challenges that lie ahead. We can overcome these obstacles through collaboration, dedication, and continued advances and fully harness the potential of cellular reprogramming.

At NecstGen, we are at the forefront of pioneering CGT research. To learn how we can help with your development and manufacturing of stem cell and gene therapies, reach out to discuss your challenges.

Related Questions

Which Cell Therapies are approved?

In these figures, we gathered and visualised overviews of approved ATMPs over the past years for you.

What does the Cell Therapy Development process look like?

From idea to treatment, you’ll face changing requirement and development challenges. View the figure to see how knowledge of the process inversely relates to freedom to make changes to your process.  

Our experts are only a message away to help you understand the impact of any of these aspects and make informed decisions on outsourcing.

We’d be happy to discuss and help you bring cell therapies to patients.

Differentiation of Human iPSCs

Differentiation of Human iPSCs

From Pluripotent to Specialized: Differentiation Pathways in Human iPSCs

Human induced pluripotent stem cells (iPSCs) offer great potential for the future of medicine. We look into the world of human iPSCs, exploring their incredible promise and the critical significance of directing their development towards specialised cell lineages. 

What are iPSCs?

Induced Pluripotent Stem Cells (iPSCs) are stem cells generated by reprogramming somatic (adult) cells to return to a pluripotent state. They possess similar attributes to embryonic stem cells (ESCs).

Human iPSCs (hiPSCs) can be differentiated into virtually any cell type found in the human body, using specific growth factors, cytokines, and substrates into mature cells.

Differentiation of hiPSCs compiles a series of steps that mimic tissue and organ formation during embryonic stages.

The Process of Differentiation

Newly formed pluripotent stem cells (PSCs) have the potential to differentiate into one of three embryonic germ layers—ectoderm, mesoderm, or endoderm—which can further develop into intermediate or terminally differentiated specialised cells.

Differentiation refers to the processes or stages in which iPSCs abandon their pluripotent stage and become committed to line-specific adult-like cell types, which can potentially be used in research and clinical applications.

 

What Influences iPSC Differentiation?

Various external factors must influence iPSCs’ change for them to successfully undergo the various stages of differentiation.

Growth Factors and Cytokines

Growth factors and cytokines are used as signalling molecules that govern the fate of iPSCs directing them along developmental trajectories. 

Growth factors such as BMPs, FGFs, and Wnts orchestrate the activation of specific signalling pathways and the expression of lineage-specific genes. 

Cytokines influence the behaviour of iPSCs, although not all differentiation processes depend on these external factors for successful specialisation. For instance, interleukin-6 (IL-6) can influence the differentiation of iPSCs into certain immune cells, demonstrating the specific effects of cytokines in stem cell biology.

3D Culture Systems and Organoids

3D culture systems and organoids offer a physical and structural advantage in replicating in vivo conditions and, in some cases, can enhance the efficiency of iPSC differentiation. 

Unlike traditional 2D cultures, these three-dimensional environments provide iPSCs with spatial cues and interactions that more closely mimic native tissues. This fosters accurate differentiation and encourages the formation of complex tissue structures formed by two or more cell types, enabling the study of organ-specific functions and diseases. 

Co-culture Techniques

Co-culture techniques involve growing iPSCs in the presence of other cell types or within a specific cellular microenvironment.

In some co-culture systems, iPSCs are grown directly with other specific cell types to promote differentiation. This approach aims to mimic the natural cellular interactions and signals in the body, enhancing the differentiation, maturation, and functionality of the iPSC-derived cells. On the other hand, when co-cultures involve cell types from different organs, removing the nurturing cell type component is necessary if cells are intended for functional studies or clinical use.

Differentiation into Key Lineages

IPSC differentiation aims to transform iPSCs into specific, functional cell types. This differentiation is essential for advancing regenerative medicine, disease modelling, and drug discovery. The lineages described below are highlighted due to their broad applications and significant impact in current research and therapy development. However, it’s important to note that other lineages, such as lymphopoietic lineages which are crucial for producing allogeneic CAR T cells, also play critical roles in medical science.

Neural Lineages – Initially, hiPSCs are guided to adopt an ectodermal fate, the germ layer from which the nervous system originates. Subsequently, they can be coaxed into neural progenitor cells and further differentiated into mature neurons, astrocytes and glial cells.

Cardiovascular Lineages – The differentiation of hiPSCs into cardiovascular lineages, including cardiomyocytes, smooth muscle cells, endothelial cells and cardiac fibroblasts, involves sequential steps that lead hiPSCs towards a mesodermal fate, the precursor to heart cells. Activation of specific cardiac transcription factors eventually yields functional components of the cardiovascular system. 

Hematopoietic Lineages – hiPSCs can be differentiated into various blood cell types, such as erythrocytes, platelets, and immune cells, mimicking the hematopoietic lineage. The process commences with hiPSCs adopting a mesodermal fate and progressing towards hemangioblasts, common precursors for endothelial and blood cells.

Endodermal Lineages – hiPSCs can be directed towards endodermal lineages to generate cell types found in internal organs like the liver and pancreas. The result is the production of functional hepatocytes, pancreatic beta cells, and other organ-specific cell types.

Mesenchymal Lineages—Mesenchymal stem cells (MSCs) derived from hiPSCs are developed by guiding iPSCs towards a mesodermal fate. These cells can differentiate into osteoblasts, chondrocytes, and adipocytes. iPSC-derived MSCs provide a potentially unlimited supply for both autologous and allogeneic cell therapies, overcoming the limitations of donor-derived MSCs.

Challenges and Limitations in iPSC Differentiation

Although the differentiation of hiPSCs into various cell types holds tremendous potential for regenerative medicine, disease modelling, and drug discovery, the processes involved in iPSC differentiation face several challenges and limitations that researchers are actively working to overcome.

Ensuring the Purity of Cell Populations

One of the foremost challenges in iPSC differentiation is ensuring the purity of the resulting cell populations. 

Although iPSCs possess the remarkable capacity to differentiate into various cell types, this pluripotency can lead to a heterogeneous mix of cells. Researchers face the intricate task of refining differentiation protocols to obtain homogenous populations of desired cells while minimising the presence of off-target cell types. 

This complexity necessitates constantly optimising differentiation protocols and novel cell sorting and enrichment techniques.

Recapitulating in vivo Development

Another significant challenge is replicating the conditions and timelines of natural human development in vitro. 

In vivo development is a finely tuned process influenced by a multitude of factors, including spatial and temporal cues, signalling pathways, and epigenetic modifications. Recreating these intricate dynamics in a culture dish is a formidable task. 

Researchers must develop precise differentiation protocols that mimic the in vivo microenvironment to accurately guide iPSCs toward the desired cell fate.

Functional Validation

Beyond appearances, it is vital to ensure that the differentiated cells do not merely look the part but also function effectively and safely when transplanted. 

Functional validation is a critical aspect of iPSC differentiation. Researchers need to assess differentiated cells’ functionality, maturity, and stability through rigorous quality control measures and functional assays, thus ensuring that iPSC-derived cells can perform their intended roles in therapeutic applications or disease modelling.

The Future: Advancements in Differentiation Protocols

With induced pluripotent stem cell (iPSC) research moving rapidly, researchers are actively exploring innovative approaches and leveraging cutting-edge technologies to develop more efficient, scalable, and precise differentiation processes.

Advanced cell culture systems represent a significant avenue of progress. Researchers are working to enhance culture substrates, employ three-dimensional (3D) culture techniques, and use microfluidic systems to better mimic the native microenvironment of developing tissues and organs.

Gene editing technologies, such as CRISPR-Cas9, are also crucial in shaping the future of iPSC differentiation. These tools enable precise manipulation of iPSCs’ genetic makeup, guiding them toward specific lineages and allowing researchers to optimise differentiation protocols, minimising the occurrence of off-target cell types.

Small molecules and signalling pathway modulators are increasingly critical in directing cell fate during differentiation. Researchers are using these chemical tools to exert precise control over cellular processes, enabling the greater accuracy of generating homogeneous populations of desired cell types.

Machine learning algorithms and computational biology are helping to analyse extensive datasets generated from techniques like single-cell RNA sequencing. This data-driven approach helps uncover novel insights into differentiation processes, assisting researchers in refining protocols and identifying critical regulators of cell fate.

Combined with advancements in automation and scale-up techniques, they are pivotal for translating iPSC differentiation protocols into clinical applications. Scalable bioreactors and automated systems enable the production of large quantities of differentiated cells, a crucial aspect for therapies and drug screening on a larger scale.

Conclusion

The differentiation journey in induced pluripotent stem cells (iPSCs) is central to realising their immense therapeutic potential.

With ongoing research and technological advancements, iPSC differentiation is set to achieve more efficient, precise, and scalable differentiation protocols. These developments are poised to revolutionise how we approach various medical conditions and create unprecedented opportunities for personalised medicine.

At NecstGen, we are actively working in the field of iPSC research. To learn how we can help with your development or manufacturing of stem cell and gene therapies, reach out to discuss your challenges.

Related Questions

Which Cell Therapies are approved?

In these figures, we gathered and visualised overviews of approved ATMPs over the past years for you.

What does the Cell Therapy Development process look like?

From idea to treatment, you’ll face changing requirement and development challenges. View the figure to see how knowledge of the process inversely relates to freedom to make changes to your process.  

Our experts are only a message away to help you understand the impact of any of these aspects and make informed decisions on outsourcing.

We’d be happy to discuss and help you bring cell therapies to patients.

iPSC Development: Technical, Clinical, and Regulatory Hurdles

iPSC Development: Technical, Clinical, and Regulatory Hurdles

The Complexities of iPSC Development

Induced pluripotent stem cells hold immense promise in revolutionising medicine through patient-specific therapies. However, their clinical development presents intricate challenges, including safety validation, differentiation complexities, and ethical considerations to consider.

The Potential Applications of iPSC Therapies

Induced pluripotent stem cells (iPSCs) represent a significant breakthrough in regenerative medicine, heralding new possibilities for treating diseases once thought incurable.

These versatile cells can potentially treat various health conditions and provide insights into disease mechanisms. The unique characteristic of induced pluripotent stem cells (iPSCs) is that they can be derived from a patient’s cells, enabling researchers to develop disease models. This advances more precise drug testing and the formulation of personalised treatment strategies.

iPSCs are also revolutionising personalised medicine, enabling tailored regenerative therapies and advancing research and development. They facilitate the creation of patient-specific cells for repairing damaged tissues, studying disease, and developing immunotherapies, thus heralding a new era of targeted and effective medical interventions.

The Technical & Scientific Challenges of iPSCs

While iPSC-based therapies may offer unprecedented opportunities for some of the applications listed above, there are plenty of technical challenges to consider.

The Genetic Integrity Conundrum

Reprogramming somatic cells into iPSCs can introduce unwanted mutations. These genetic aberrations can compromise the functionality and safety of iPSC-derived tissues. 

For researchers, the challenge is finding a way of maintaining genetic fidelity throughout the iPSC generation process, while still navigating the need for rigorous quality control measures to minimise the risk of introducing detrimental mutations.

Proliferation and Teratoma Risk

A unique property of iPSCs is their ability to proliferate indefinitely (self-renewal), yet this self-renewal capacity can become a double-edged sword when iPSCs are used for transplantation. 

The risk of teratoma formation is concerned with using cells derived from induced pluripotent stem cells (iPSCs), not with the iPSCs themselves. When iPSCs are differentiated into specific cell types before implantation, the challenge lies in ensuring these cells do not proliferate uncontrollably. Balancing cell expansion to prevent unwanted growth is critical to developing safe iPSC-based therapies.

Integration & Immuno-compatibility

Successfully delivering iPSC-derived cells to target tissues and ensuring their integration within the host environment present substantial hurdles. 

Precise delivery and engraftment techniques are critical to maximise the therapeutic benefits of iPSC-based therapies. The challenge lies in achieving the correct location, timing, and interaction with the host tissue.

To compound this further, even when iPSCs are derived from a patient’s cells (autologous iPSCs), immunological responses can still occur when iPSC-derived tissues are transplanted, potentially leading to rejection. 

Strategies to enhance graft survival, such as immune modulation and engineering techniques, are being developed to address this nuanced challenge.

Mastering Cellular Fates: Challenges in Directed Differentiation

Efficiently coaxing iPSCs into desired cell lineages and ensuring their subsequent maturation and functionality is complex. Differentiation protocols must be finely tuned to yield high-quality, functional cells. 

Researchers face hurdles in optimising protocols, to prevent suboptimal outcomes that limit the therapeutic potential of iPSC-derived cells.

While induced pluripotent stem cells (iPSCs) possess remarkable and offer prospects for personalised treatments and tissue regeneration, several complexities surround their use. These include issues related to the lack of maturity of iPSC-derived cells, which do not consistently achieve full functionality equivalent to their adult cell counterparts. Additionally, the challenges extend to ensuring the safety, ethical considerations, and control of cell differentiation. As the scientific community progresses in addressing these challenges, iPSC-based therapies may become a cornerstone of patient-specific medical treatments.

 

Regulatory & Ethical Considerations

In addition to the technical and scientific challenges of iPSCs, there is also a strong need for regulatory and ethical considerations. Stringent regulations are required for approval, as are the ethical considerations that include informed consent and protecting patient well-being.

Rigorous safety assessments through each stage of clinical trials are imperative to address concerns like tumorigenicity, and immunogenicity can only be achieved through clear experimental endpoints with robust release criteria.

Ethical Minefields

Complex ethical debates emerge with the use of iPSCs. Potential modifications using iPSC-derived germ cells raise ethical questions about altering the human genome in ways that could impact future generations. These concerns highlight the need for careful consideration of the long-term effects and the ethical implications of such genomic interventions. The unpredictability of unforeseen long-term consequences associated with iPSC therapies adds further ethical dimensions. 

Ethicists, researchers, and policymakers must engage in thoughtful discourse to navigate the promise of iPSCs in medicine with the responsibility to safeguard against unforeseen consequences and maintain ethical integrity.

Contrasting iPSCs with Other Stem Cell Modalities

Contrasting iPSCs with other stem cell modalities reveals a compelling comparative perspective, highlighting the distinct developmental complexities inherent in each approach. 

iPSC therapies – while patient-specific and ethically sound – present challenges related to differentiation and tumorigenicity. In contrast, embryonic stem cells (ESCs) offer robust differentiation potential but come with ethical concerns regarding embryo use. 

Adult stem cells (ASCs) are less versatile in differentiation but generally raise fewer ethical issues.

Potential Innovations and Solutions

To advance the potential of iPSCs, new technologies and techniques must continue to evolve with the latest research.

Next-Gen Reprogramming

Ongoing research is driving the evolution of reprogramming methods towards safer and more efficient approaches in regenerative medicine. 

This next generation of reprogramming techniques focuses on enhancing safety by reducing the risk of genetic mutations and tumorigenicity associated with iPSCs. Simultaneously, researchers strive for greater efficiency, streamlining the reprogramming process to produce iPSCs more rapidly and precisely. 

These advancements promise to accelerate the development of personalised therapies, minimise potential risks, and broaden the scope of iPSC-based treatments. As technology continues to advance, the future of reprogramming holds the potential to revolutionise regenerative medicine.

Synergy with Advanced Therapeutics

Integrating iPSCs with therapies like CRISPR-based gene correction opens a realm of unprecedented possibilities in medicine. These synergies leverage the regenerative potential of iPSCs with the precision of CRISPR to address genetic diseases at their roots. 

iPSCs can be engineered using CRISPR to correct or replace defective genes, offering patient-specific, customised treatments. This approach holds immense promise for previously incurable genetic disorders. 

Furthermore, iPSCs can serve as a renewable source for generating cells for transplantation, enhancing the safety and efficacy of cell-based therapies. The convergence of iPSCs and CRISPR represents a groundbreaking frontier, propelling medicine towards more precise, effective, and personalised therapeutic interventions.

Conclusion

The promise of iPSC therapies is set to revolutionise scientific and medical applications. iPSCs offer hope for countless individuals suffering from diseases once deemed untreatable, signalling a future where personalised medicine could become the standard, not the exception.

Yet, this promise comes with its share of intricacies. The path to realising the full potential of iPSC therapies is a tapestry woven with scientific, ethical, and regulatory aspects, each adding its complexity to the challenge. 

At NecstGen, we are dedicated to accelerating safe and effective cell and gene therapy applications. To learn how we can help with your development or manufacturing of stem cell and gene therapies, contact us to discuss your challenges.

Related Questions

Which Cell Therapies are approved?

In these figures, we gathered and visualised overviews of approved ATMPs over the past years for you.

What does the Cell Therapy Development process look like?

From idea to treatment, you’ll face changing requirement and development challenges. View the figure to see how knowledge of the process inversely relates to freedom to make changes to your process.  

Our experts are only a message away to help you understand the impact of any of these aspects and make informed decisions on outsourcing.

We’d be happy to discuss and help you bring cell therapies to patients.

EIC Awards €2.5 Million Grant

EIC Awards €2.5 Million Grant

European Innovation Council Awards €2.5 Million Grant to Trince, NecstGen, and IBSAL for Advancing Cell Therapy Manufacturing

[Ghent, Leiden, Salamanca, 15/03/2024] – Following a rigorous selection process by an expert panel, Trince, NecstGen, and IBSAL are proud to announce that their “Penphomet” project has been selected by The European Innovation Council (EIC) for a significant grant of €2.5 million. Out of 257 eligible submissions, Penphomet is one of the 27 that has been awarded. Led by Trince, the consortium aims to revolutionize cell therapy manufacturing by integrating nanotechnology, optics, and microfluidics.

Cell therapy has shown promising results in cancer treatment, specifically using patient-derived cells like T cells and mesenchymal stromal cells (MSCs) that have been genetically engineered to effectively target cancer cells.

The primary focus of the Penphomet project is to develop a safer, non-viral method for cell engineering that minimally impacts cell functionality and phenotype. The aim is to significantly reduce the costs associated with cell therapy manufacturing.

Over three years, the project aims to deliver a fully automated, high-throughput system that can be installed in centralized cell production facilities or integrated into point-of-care cell manufacturing equipment.

“We are grateful for the EIC’s support in funding the Penphomet project. It demonstrates that our breakthrough technology is addressing a crucial gap in the field of cell therapy,” said Philip Mathuis, CEO at Trince. “Together with our partners NecstGen and IBSAL, we are committed to advancing cell therapy manufacturing, ultimately benefiting patients and healthcare systems.”

“NecstGen is proud to be a part of the Penphomet consortium supporting the further development of the innovative technology of Trince. Non-viral methods for cell engineering represent a potentially cost saving route for cell engineered therapies. And furthering their use is important for the field of Cell and Gene Therapy and mission of NecstGen to enable patient access” said Paul Bilars, CEO, NecstGen.

“For the IBSAL and its main partners, the University Hospital and the University of Salamanca, the Penphomet project opens the possibility of exploring a new strategy of cell modification that can be enormously attractive for the next generation of advanced therapy medical products, and we are really pleased to be part of this initiative,” says Prof. Fermin Sanchez-Guijo, principal investigator of the IBSAL in this project.

The Penphomet project represents a significant advancement in improving the accessibility and affordability of cell therapies, with the potential for far-reaching impacts on cancer treatment and beyond.

For media inquiries or further information, please contact:

[Philip Mathuis]

[Trince]

[+32 9 273 56 25]

[info@trincebio.com]


Trince

Trince offers a unique intracellular delivery (transfection) technology for the life sciences/biotech field. The LumiPore platform is based on the interaction between pulsed laser light and photothermal nanomaterial. By irradiating the proprietary nanoparticles with laser light, highly localized light-induced thermal and mechanical forces are generated. When these forces come into contact with the cell membrane, they create temporary pores through which external effector molecules can enter the cell. This ‘photoporation’ technology was developed as a next-generation intracellular delivery platform for efficient, flexible gentle, and safe delivery of a wide variety of effector molecules in a broad range of primary and hard-to-transfect cells, while maintaining high therapeutic quality. The technology can deliver a diverse set of payloads in various hard-to-transfect cell types, including suspension and adherent cells (directly in a standard lab recipient) and even living tissue slices.

NecstGen

NecstGen is a non-profit CDMO and centre of excellence for Cell and Gene Therapy, located in a purpose-built GMP facility on the largest bio-cluster in the Netherlands, Leiden Bio Science Park.  NecstGen provides critical contract development, manufacturing and rental services to academic and industrial therapy developers to deliver a new generation of therapies to patients.

NecstGen offers:

  • Full contract manufacturing services for Cell Therapy and Viral Vector
  • Process design, scale-up, optimisation and automation for Cell Therapy and Viral Vector
  • Assay development for in-process, release, and potency
  • Cleanroom rental including services for QA, QC, and QP.

IBSAL

The Institute of Biomedical Research of Salamanca (IBSAL) is part of IECSCYL (The Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León) and is one of the Biomedical Research Institutes accredited by the Carlos III Institute from the Spanish Ministry of Health (Order of February 17, 2014). IBSAL’s mission is to develop clinical and translational research, promoting synergy between clinical and basic research groups and optimizing resources through shared services and efficient management structures. One of the 6 areas of the Institute is Gene, Cell and Transplant Therapy, coordinated by Prof. Sánchez-Guijo. The location where the project tasks will be carried out is the Hematology Department of the University Hospital of Salamanca (HUS), also chaired by Prof Sanchez-Guijo. The Department provides services a.o. in cell therapy, includes a GMP Facility and a Translational Research Lab, and has extensive experience in the preclinical and clinical development and management of ATMPs, especially MSCs but also CAR T cells. 

EIC Transition projects focus on results generated by EIC PathfinderFET (Future and Emerging Technologies – as the predecessor of EIC Pathfinder)  or European Research Council (ERC) Proof of Concept projects, to mature the technologies and build a business case for specific applications. Grants of up to €2.5 million are available to validate and demonstrate technology in application-relevant environment and develop market readiness. 

Cell Therapy Manufacturing & Development

Viral Vector Manufacturing & Development

Cleanroom Rental