MFX’s summer of students

Why investing time in the next generation helps give us new insights into our own technologies.

A common theme that has come up within the team at MFX is that when we were making decisions earlier on in our careers, the information about what options were available to us using our science background was often not entirely clear.

As we build out the company, we want to make sure that we are supporting the wider community by helping to build the talent pipeline entering STEM. We’re doing this by offering opportunities for visits, placements, and internships to interested students, as well as providing time for our team to engage in outreach activities. Check out our new people page to see what outreach activities our team have been up to.

At around the same time we teamed up with UCL’s ‘Manufacture and Commercialisation of Stem Cell and Gene Therapies MSc’. We welcomed the whole cohort for a tour of our facilities and some pretty intense Q&A sessions with our team leads. We loved all the insightful questions from this fantastic group – talking through our technology and gaining insights is always helpful for us!  We then welcomed Nabilla and San-Chi in our commercial and R&D teams respectively for 6-month placements.

Students from UCL’s Manufacture and Commercialisation of Stem Cell and Gene Therapies MSc

Antonio, San-Chi, and James at UCL’s Cell and Gene Therapy Research Project & Poster Session Day

Whilst MSC level students and post graduate interns are well on their way to a fulfilling career in STEM, it’s apparent that access to companies like MFX earlier on in the decision-making process can influence students make the choice to stay focussed on STEM.

Over the summer we welcomed 3 work experience students for a week – 2 from local colleges and an undergraduate student home for the holidays – and provided tours to 2 students from local schools. Here’s what they had to say about the experience.

“I am so glad that I did this work experience, I really felt like it gave such an insight into the world of small start-ups, which I had previously known nothing about… It was also great being able to see all the range of roles required to make what they do happen….. I got to discover the jobs involved that are much less technical…[and] I got to see the more traditionally technical roles expected of scientists. Seeing all these people with different skill sets come together in a really innovative environment with a common goal was inspiring to watch.“

But it’s not all one-way benefits – the students really helped us in unexpected ways:

“When you‘re so deep in new tech development, it’s really easy to forget that not everyone is as familiar with what it is you are building as you are……” says Lindsey Clarke, PhD, Commercial VP. “so having to think about how we communicate what it is we are doing to non-experts and have the students pull us up on things like internal jargon has been really helpful – being able to distil the key benefits and features of the technologies and why we are building them is really important for both our sales and marketing efforts as well as fundraising.”

Conveniently, these extra pairs of hands were available during one of our bioreactor batch assembly runs – very much a stress test opportunity for our manufacturing SOPs and training! Fortunately we passed that with flying colours – so if you’re getting involved in the MFX early access trials this autumn, the likelihood is one of our work experience students helped manufacture your Prototype bioreactor!

Yes, it requires a significant investment of time to offer these opportunities to students. But the huge value it clearly brings makes it worthwhile, and who knows, perhaps we’ll see these familiar faces as future MFX employees! Good luck to all our students and interns with their future studies and career decisions. Maybe we’re biased, but STEM is where it’s at!

From cell culture to cell therapy – the biggest challenges of growing cells ex vivo

During the development of the Cyto Engine platform we interviewed over 100 experts in cell culture and cell therapy manufacturing to understand what their biggest challenges were when culturing cells. Here’s what we found.

Cell culture is a fundamental technique in all biological research as well as in cell therapy production. It is the process of growing cells outside of their natural environment under controlled conditions and whilst it has been a cornerstone of biotechnology, pharmaceutical development, and academic research for over 100 years, the process remains complex and challenging to perform.

What did the 100 experts we interviewed highlight as being problematic? They stated contamination, reproducibility, scalability, integrated analytics, time and space constraints, and costs as pain points in their cell culture processes. These are all the problems we’ve set out to solve with the Cyto Engine.

Cell culture pain points from the 100 experts we interviewed

1. Contamination: An Ever-Present Threat

Contamination remains one of the most significant challenges in cell culture. Experts across the board emphasised the need for stringent aseptic techniques and advanced detection methods. Scientists in Pharmaceutical R&D shared the following;

Contamination can come from various sources, including bacteria, fungi, and cross-contamination from other cell lines. It can compromise the integrity of the culture, leading to unreliable data and wasted resources. This is particularly concerning when manufacturing autologous cell therapies such as CAR-T, where each batch is patient-specific and losing batches could result in a significant delay in life saving treatments. The complexity of cell therapies often involves multiple stages of cell manipulation, increasing the risk of contamination.  This is critical to avoid as there is no way of sterilising (e.g., filtering) the final product of a cell therapy (you would remove the cells you want to treat with!)

The need for ultra-clean environments, advanced contamination detection methods, and robust aseptic techniques is critical to ensure the safety and efficacy of these therapies. The industry is moving towards automation and less human touch on processes, but it will take time for meaningful changes to be enacted.

2. Reproducibility and Consistency

Another major challenge in cell culture is ensuring reproducibility and consistency across experiments. Experts from both CDMOs and biopharma companies highlighted that even slight variations in cell culture conditions can lead to significant differences in outcomes. This is particularly critical in drug development, where consistency is key to ensuring the efficacy and safety of a product.

To address this, there is a growing demand for automated systems that can precisely control and monitor cell culture environments. These systems can help reduce human error, detect important trends early (especially in terms of donor variability), and ensure that conditions remain consistent across different batches, ultimately leading to more reliable results.

3. Scalability of Cell Culture Systems

Scalability is a crucial consideration for developers involved in large-scale production of biologics, particularly for those developing cell-based therapies. As one industry leader noted:

The transition from small-scale to large-scale production often introduces new challenges such as: maintaining cell viability and phenotype, ensuring uniformity across large batches, and preventing contamination. There is a clear need for scalable bioreactors and culture systems that can accommodate these demands while maintaining high standards of quality and safety.

4. The Need for Advanced Monitoring and Analytical Tools

With the increasing complexity of cell-based therapies and growing demand for doses, the need for advanced monitoring and analytical tools is more pressing than ever. A biotech scientist emphasised the importance of real-time monitoring systems that can provide detailed insights into cell health, metabolism, and productivity:

These tools are particularly important in the development of personalised medicine, where understanding the nuances of each individual batch can make the difference between success and failure.

5. High process costs

Another critical pain point in cell culture is the high cost of reagents (e.g., media, growth factors, and supplements), which significantly impacts budgets, particularly in long-term or large-scale experiments. As mentioned by one biotech scientist:

A research institution commented:

A university researcher from the same institution highlighted:

For large-scale applications like biomanufacturing or clinical trials these expenses can quickly skyrocket, limiting the feasibility of scaling up certain experiments or processes. Even routine cell culture maintenance becomes a costly affair when working with large volumes or sensitive cells that require expensive additives. One pharma manufacturing expert highlighted the need for:

To address these high costs, researchers are exploring several strategies such as optimising media compositions to use fewer expensive components, or adopting serum-free media, which often lowers costs in the long term. Automation can further optimise reagent use, minimising waste and ensuring more efficient use of costly materials.

6. Time and space constraints

One of the biggest challenges is the large amount of time and space needed to cultivate cells, particularly when scaling up for clinical applications. Traditional T-flasks require significant incubator space, limiting how much can be done at any given time. In addition, manual processes in cell culture, such as media changes, cell counting, and passaging, are time-intensive and increase the risk of human error. The need for constant attention to ensure optimal growth conditions can be overwhelming.

One scientist at a research institution mentioned that:

Additionally, we heard about IPSC culture:

Automation and miniaturised systems are increasingly being adopted to maximise space and optimise growth conditions. These systems enable researchers to grow more cells in less space without compromising efficiency.

Conclusion: A Collaborative Effort

Addressing these challenges requires a collaborative effort across the life sciences industry. From academia to big pharma, and from small biotech start-ups to global CDMOs, the need for innovation and collaboration has never been greater. By sharing knowledge and resources, the industry can develop the tools and techniques needed to overcome these hurdles, ultimately leading to more effective therapies and better outcomes for patients.

The insights we gathered from industry leaders underscore the importance of continued investment in research, technology, and infrastructure to address the complex challenges of cell culture. As we move forward, it is clear that the future of cell culture lies in a combination of advanced technology, rigorous standards, and a commitment to continuous improvement.

Cutting the cost of CAR-Ts – Innovative strategies to make cell therapies more affordable

T cells are the most extensively studied cell type in the development of cell therapies, constituting 58% of active UK ATMP clinical trials (1). CAR-T (Chimeric Antigen Receptor T cell) therapy uses synthetically engineered receptors targeting a specific ligand in T cells to target and destroy tumour cells. Following three decades of development (2), CAR-T therapy has shown significant benefits in patients with B cell malignancies (3), and is being explored for broader indications such as autoimmune disease.

Currently, commercially available CAR-Ts are predominantly autologous therapies, being made for individual patients by extracting their T cells and modifying them in the lab. CAR genes code genetically engineered proteins that fuse an antigen recognition domain from a monoclonal antibody with the intracellular T cell signalling and costimulatory domains of the T cell (4). These proteins are then expressed on the surface of the T cells.

Major Steps in CAR-T Manufacturing Process (5,6)

CAR-T therapies typically take around 1-2 weeks to create, although exact processes can differ depending on the provider. Generally, the procedure involves:

• Leukapheresis

The patient’s T-cells are extracted using a separation process called leukapheresis, which collects cellular components from the blood. They are then sent to the manufacturing facility which may require them to be cryopreserved for transport.

• T-cell Selection & Activation

T cells are further purified from the leukapheresis and then activated using CD3/CD28 co-stimulatory antibodies or activation reagents and cytokines.

• Gene Transfer (Transduction or Transfection)

Viral vector is added to the T cells, or for non-viral approaches, electroporation or other novel techniques can be used to insert genes into the cell

• T-cell Expansion, Formulation & Cryopreservation

T cells are expanded to the required number of cells for a dose. Harvested cells are then cryopreserved for transport.

• Transport and Patient Administration

CAR-T cells are transported from a central manufacturing site to the hospital/medical centre and administered to the patient.

Despite the well-established protocols of production and high efficacy of these therapies, CAR-Ts only reach a limited number of patients. This is largely due to the cost, with the price of CAR-T therapies often reaching £400,000 per patient (8). One way to tackle these costs is by optimizing the current manufacturing process.

A variety of strategies are being investigated to reduce the expenses of CAR-T therapies. Some companies (1) are developing new technologies to automate parts of the manufacturing process, reducing labour costs and human error. A wider conversation within the cell and gene therapy (CGT) industry is looking at decentralised manufacturing, producing therapies at the point of care (9,10) or even in the patient themselves, removing the need for ex vivo manufacturing and reducing logistical costs.

The benefits and drawbacks of various CAR-T manufacturing strategies (7)

There is no single solution to make CAR-T therapies more affordable. However, the ongoing development of strategies to reduce manufacturing costs is a promising step to making these innovative and life-changing therapies available to everyone who needs them. worth waiting.

At MFX, we’re developing our Cyto Engine technologies to seamlessly scale up or down. This allows a greater understanding of the biology of CAR-Ts that enables faster process translation, and the ability to scale up cell numbers whilst maintaining the same microenvironment during manufacturing.

References:

1. CATAPULT, Cell and Gene Therapy. Cell and gene therapy catapult. UK ATMP Clinical Trials Report. 2022.
2. Charrot S & Hallam S. CAR-T cells: future perspectives. HemaSphere. 2019. 3:2.
3. Xin T, Cheng L, Zhou C, Zhao Y, Hu Z & Wu X. In-vivo induced CAR-T cell for the potential breakthrough to overcome the barriers of current CAR-T cell therapy. Frontiers in Oncology. 2022. 12:809754.
4. Levine BL, Miskin J, Wonnacott K & Keir C. Global manufacturing of CAR T cell therapy. Molecular Therapy: Methods & Clinical Development. 2017. 4: 92-101.
5. Wang X & Riviere I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Molecular Therapy – Oncolytics. 2016. 3: 16015.
6. Vormittag P, Gunn R, Ghorashian S, Veraitch FS. A guide to manufacturing CAR T cell therapies. Curr Opin Biotechnol. 2018;53:164-181.
7. Ayala Ceja M, Khericha M, Harris CM, Puig-Saus C, Chen YY. CAR-T cell manufacturing: Major process parameters and next-generation strategies. J Exp Med. 2024;221(2)
8. Tumaini B, Lee DW, Lin T, Castiello L, Stroncek DF, Mackall C, et al. Simplified process for the production of anti-CD19-CAR engineered T cells. Cytotherapy. NIH Public Access; 2013; 15(11):1406.
9. Lopes AG, Noel R, Sinclair A. Cost analysis of vein-to-vein CAR T-cell therapy: automated manufacturing and supply chain. Cell Gene Ther Insights. BioInsights Publishing, Ltd.; 2020; 6(3):487–510.
10. Orentas RJ, Dropulić B, Lima M de. Place of care manufacturing of chimeric antigen receptor cells: Opportunities and challenges. Semin Hematol. W.B. Saunders; 2023; 60(1):20–4.

Embracing Inclusivity: The CGT Circle X Pride – A Recap of The CGT Circle’s First-Ever Workshop

Last month The CGT Circle held it’s first ever workshop event at Stevenage Bioscience Catalyst (SBC), supported by MFX and SBC and facilitated by The Honeycomb Works. A session focussed on building and sustaining truly inclusive cultures. This event was not just informative but incredibly engaging and sparked much enthusiastic and thought provoking discussions.

Leaders from various startups, James Kusena PhD (VP of Operations & Product Owner at MFX); Sheila Johnson (HR Consultant); and Pedro Correa de Sampaio (CEO of Neobe Therapeutics), shared their insights on putting inclusion into action, even while navigating the high-pressure world of securing funding and driving impactful change. It was motivating to hear their real-world experiences and challenges, and how they strive to create inclusive environments in their organizations. 

The guests weren’t just passive listeners, they got to collaborate on practical exercises. It was a hands-on opportunity to put some of the ideas discussed into action. The activities were designed to help the audience gain a tangible understanding of what they can do to start building an inclusive culture in their own spaces, whether at work or in communities.

Some of the key takeaways that can help to make a real impact:

1. Creating an intentionally inclusive culture requires specific actions and policies. The workshop emphasized the importance of communicating expected behaviors, holding individuals accountable for bad behavior, and establishing well-defined policies and processes. A public commitment to inclusivity will reinforces the organization’s dedication and accountability to fostering a respectful and inclusive environment.

2. Inclusive recruitment, a crucial area for impactful change, involves ensuring a fair hiring process that attracts diverse candidates. Implementing to a structured recruitment process minimizes biases and maintains consistency. Actively engaging with initiatives to increase diversity in STEM widens the talent pool, while regularly collecting data and feedback identifies areas for improvement and measures progress.

3. Supporting managers in promoting an inclusive culture is essential. Inclusion should be integral to their role, with clear behaviors provided as a guide. Regular conversations and support help them navigate challenges, and including inclusivity in performance reviews ensures accountability and rewards their efforts.

4. Regularly measuring the impact of inclusivity efforts is crucial. Observing behaviors and gathering feedback on how people feel about the workplace can boost success. Collecting aggregate and demographic data early on helps establish a baseline, track progress, and identify areas needing more focus

We were delighted to support this event and look forward to hearing more from The CGT Circle and The Honeycomb Works on these important topics!

How to Innovate? The MFX way

Césaré Cejas, PhD gave a recent talk at the Bioengineering Symposium, a jointly organised event held by the Oxford University Bioengineering Society and Warwick BioSoc on the topic of “conceptualising innovations to confront current challenges in cell and gene therapy.

Here’s some of his key learnings from co-founding and building MFX to where it is today!

Understand the industry

To precisely define your problem. What are the current challenges in the CGT industry? Scalability is definitely on top of list to properly translate process development to high-throughput manufacturing without the need for process re-optimisation. MFX leverages the geometric form factor to ensure fluid streamlines are identical in small and larger scales. How the fluid (media) interacts with the cells can significantly affect shear, which in turn affects cell expansion.

Know your customer

To give voice & value. Identify your potential user and understand the pain points in their process and ask them about their “ wishlist.” In an ideal world, what do they seek in terms of hardware that improves their process? In MFX , we leverage understanding things at a small scale to make process improvements at a large scale: scale-down to screen, then scale-up and scale-out.

Know your landscape 

To know your position and market offering. Understand what others are doing in the space to develop strategy, which products/customers to keep satisfied, manage closely, monitor, or keep informed. When it comes to bringing something new to any market, resistance is expected but education and information help enable adoption of new innovation.

Design, validate, iterate

Rinse and repeat. Assess information from customers and competitive landscape, and iterate technology accordingly, making sure there is market need. Innovation needs to have a purpose. One can have the most ingenious idea but if customers don’t find a use for it, it then does not provide value for them and it’s not “innovative.”

Build relationships

Network to stress-test the innovation. The CGT industry is built on relationships. A lot of the processes are relatively new and experimental, and because of ongoing challenges relating to optimisation and scalability – there is appetite for new innovation that improves accessibility and improves the journey from discovery/screening to commercialisation.

The Best Cell and Gene Therapy Conferences in 2024

What are the best Cell and Gene Therapy conferences to attend in 2024?  We asked our VP of Commercial Lindsey Clarke what her top picks are for the coming year.

It really depends on what your reasons are for wanting to attend an event. Do you have some exciting data that you want to share with the community? Are you looking to find out about the latest trends in technologies or what exciting things are happening in the industry? Is it to get an understanding of the bigger picture macro environment that could help with your work? Is it to get an idea of the latest trends in relation to the specific cell or vector types you are working with? Or is it that you’re looking to connect with others working in the industry and build your own personal network?  Each and every one of these is a valid reason for attending an event. But depending on your reason – there are different events which would suit you best.

ISCT, ASCGT, and ESCGT – keeping up with the latest scientific advances

At the same time as enjoying winter sun in between meetings, January is also the time to polish up abstracts for the big scientific society meetings that are coming up in May in North America – ISCT and ASGCT.  The society meetings tend to be widely attended by the technical crowd and those running the early clinical trials, so there’s many of the scientists involved in basic research in academia and industry, as well as data from the clinic.  Lots of posters and talks on science and clinical progress make these events a great opportunity to find out what’s happening in the field. They’ll also be well attended by technology suppliers so you can find out about the latest pieces of kit that could help your research. And if you can’t justify the transatlantic flight, Europeans can look forward to their regional ISCT event and ESGCT in the latter part of the year.

Advanced therapies – a UK-based CGT event

Another global event that happens early in the year is Advanced Therapies in London. The ExCel is a vast events centre in east London, conveniently connected via the Elizabeth line direct to Heathrow.  With London being such a hub of cell therapy, there’s always a strong local crowd as well as many international guests.

Meeting on the Med and Mesa – bringing key stakeholders together on both sides of the pond

If connecting with colleagues globally is important for you then it might be worth looking into the work of the Alliance for Regenerative Medicine which is the leading international advocacy organization for the industry and brings together many key stakeholders.  It also holds two large events annually – one each side of the pond – Meeting on the Med and Meeting on the Mesa!

CAT-TCR – drilling into the details within cell therapies

If you’re looking for scientific detail, then events focussing on cell types such as CAR-TCR by Hanson Wade provide a more narrow scope, meaning you’ll get to meet others working in very similar fields.  Other niche events include important topics around manufacturing, analytics, regulations, supply chain, and automation.  By attending a niche event you’ll be guaranteed an audience equally interested in the event’s topic.

Alternatively if you want to learn from the broader bioprocessing community, then often the large bioprocess industry events have a cell and gene therapy manufacturing stream to them.

To round up  – there are so many events which offer different things depending on what you’re looking for. You may want to mix up your conference schedule to include some big showcase general events that cater to the whole industry for broad updates and learnings, some local events to meet with the industry in your part of the world, and some really niche events to focus on the deep science of your area of interest.

Where can you find MFX in the next few months?

• January 10-11 2024 – ESACT-UK, Stevenage
• January 16-19 2024 – Advanced Therapies Week, Miami
• February 27-29 2024 – CAR-TCR, London
• March 19-20 2024 – Advanced Therapies, London
• May 29-20 – ISCT, Vancouver