Over the last decade, the field of cell therapy has expanded rapidly. However, while there are now more cell therapies on offer than ever before, there are a number of factors that are still preventing them from becoming widely used.

Cell therapy holds enormous promise for treating many different diseases. It has also been the cause of controversy regarding the source of the cells, for example, in the case of therapies using embryonic stem cells. Recent fraud cases, such as the Harvard scandal in the US last year, have also been problematic for the area.

Some forms of cell therapy, such as hematopoietic stem cell transplantation to treat certain types of cancer, have been around since the 1950’s. While the potential of other types of cell therapy has been known for a while, it has only been in recent years that the field has really started to expand.


With the first CAR T-cell therapies (technically a combination of gene and cell therapy) to treat blood cancers gaining US and European approval last year and global investment of over €6.7B in cell therapy in 2018, the question on everyone’s lips is ‘is cell therapy about to hit the big time?’

Cell therapy - Total 2018 Global Financings

Before this can happen there are some teething problems that need to be ironed out. Cells are biological material and notoriously unpredictable to grow and transport. Setting up a reliable, consistent and scalable manufacturing system is key to producing cell therapy on a wider scale. If this problem can be cracked, then another issue currently preventing mass roll out might also be at least partly solved, namely, that of excessively high pricing.

Finally, ensuring these therapies are safe for patients and adequately regulated, as well as ensuring health care professionals know how to use them is something else that must be tackled.

I spoke to several experts in these different areas to find out how close we are to mass rollout of these new and exciting therapies and what can be done to speed up the process.

Navigating the manufacturing maze

Research and development in the sector is undeniably booming, but growing, sourcing and transporting cells and other components for these therapies can be tricky. There is a definite manufacturing bottleneck in the market for researchers and biotech companies trying to produce different cell therapies.

This has created an opening for a number of innovative companies to come along and bridge this gap. For example, French biotech TreeFrog Therapeutics has created a 3D alginate encapsulation system that allows stem cells to be cultured and also transported in the optimum environment for their growth.


“In some ways, we are a new generation of cell therapy companies,” Kevin Alessandri, CEO at TreeFrog, told me. “We aren’t directly in cell therapy. We are providing technical platforms so that they can then be implemented. It seems that for now, there are no main players that can do everything. There are very many players working together to bring solutions to the patients. That’s our feeling.”

Cell Therapy - Manufacturing Clean Room

Cell Therapy - Manufacturing Clean Room

They are not the only ones, with UK companies such as Cytera Cellworks and Oxford Genetics also tackling manufacturing issues such as automation and scaling up cell therapy production.

Alan O’Connell, Partner at Irish life sciences VC Seroba, agrees that manufacturing can be a sticking point and says it is something he and his colleagues look at when deciding to invest in a company or not. “If there is a lack of understanding of the complexity involved, I think that clearly would be a red flag for us looking at any company in the space,” he explained.

“Some of the companies have a significant naivety in terms of the complexity, so they focus very much on getting that initial clinical trial started and have spent very little time thinking about how scalable it is and what the inputs are, and whether the process been streamlined from a more efficient perspective or not.”

Darren Disley is CEO of a new cell therapy biotech called Mogrify, based in Cambridge in the UK. He believes there are still some issues to be solved with the production of cell therapies, but that the situation is much better than it was.

“The technologies are coming together to speed up and simplify the process. People don’t need to buy into the concept of an autologous therapy – taking your own cells and acting as a donor. They don’t need to buy into the concept of a universal cell therapy. They’re more into the execution challenges of how to make a complex cell like a T cell behave universally,” he told me.  

Tackling the affordability issue

Cell therapies, particularly gene-edited cell therapies such as cancer-targeting CAR T-cells, are notoriously expensive. The field is still in an early stage, and the complex manufacturing that these biological treatments require means that their price is currently at a premium.

For example, the two CAR T-cell therapies — Yescarta and Kymriah — that were approved in the US and Europe last year have been given price tags of $373,000 (€332,764) and $475,000 (€423,773), respectively, in the US, with similar pricing in Europe.

Cell Therapy - CAR T-cell process

Cell Therapy - CAR T-cell process

“In terms of the first-generation technologies, there probably is a tolerance for higher pricing for a period. Particularly for rare diseases with a very small subset of patients,” O’Connell commented. Although he notes that as patient populations go up these prices will just not be sustainable in the long term.

“The manufacturing and the cost of manufacturing are a huge issue here. If you can streamline that whole manufacturing process, improve the logistics, the supply chain, increase the yield, that will obviously impact significantly in terms of the cost of goods and the complexity of getting the product to the patient and that will help bring down the cost.”

Jacqueline Barry is the Chief Clinical Officer at the Cell and Gene Therapy Catapult in the UK, which is a government funded organization that helps bridge the gap between science and industry in this area. She agrees that reducing manufacturing costs is of key importance, but adds that finding novel methods of reimbursement is also key.“These products potentially are transformative and curative, but we don’t know yet. They have not been used for long enough,” she told me.

Barry was involved in setting up the three Advanced Therapy Treatment Centres now running in the UK with the aim of getting cell and gene therapies to patients around the country in the fastest and most cost effective way possible. She explained that a number of different payment schemes are being considered to roll out these therapies across the UK, including one that involves spreading the payment out over time to better share the risk of the therapies failing.

“Say there was a five-year follow-up, each year, there would be a risk-sharing mechanism where the first year, the developers would get 20%. Then, if the patient was still alive the following year, they’d get the following 20% and so on. The NHS isn’t paying for something upfront when it doesn’t know whether it’s effective yet, but the manufacturer does have a way of getting a full reimbursement.”

How to regulate living therapies

A key concern about cell therapies is ensuring they are safe and effective for patients. How best to regulate these novel therapies, but also to get them to market as quickly as possible, has been challenging for official bodies such as the EMA and the FDA.

“I think now people are getting their heads around it and they’re seeing a more streamlined pathway. With cell therapy… it’s not like we have to show every mechanism of action, on and off target, but you have to show the phenotype and you have the show the safety,” commented Disley.

“It’s a bit more challenging with a [genetically] edited cell… You are potentially producing off-target effects and things like that. There was definitely a concern there about whether there would be unintended consequences, but in a lot of cell therapies in regenerative medicine, you aren’t necessarily editing the genetic code.”

Due to the early stage of a lot of cell therapies, the main focus of the regulators is currently on ensuring patient safety. Particularly in light of some of the extreme side effects and patient deaths seen with therapies such as CAR-T cells in the early stages of their development.

Cell therapy - EMA letter

Cell therapy - EMA letter

However, the regulators are also assessing how to regulate and standardize different sections of the development process such as manufacturing and the supply chain. “I think they are responding, but probably conservatively and focusing on safety and efficacy first,” noted O’Connell.

He believes the next step for regulators will be the standardization of the regulations around manufacturing, quality control, supply chain and input material. “I think that’s one of the big issues – ensuring that you have a consistency of the quality of the material,” he emphasized.

The US regulators are currently in the lead when it comes to keeping up with the research and being open to changing their processes, according to O’Connell. Although he says Europe is not too far behind. “Certainly, the EMA is responding, but from my perspective, the FDA is taking the lead, at least currently.

Is 2019 the year cell therapy will hit the big time?

At the end of 2018, there were 33 ongoing phase III clinical trials of cell therapies and 16 of gene-modified cell therapies such as CAR T-cell therapies around the world. Global investment in both kinds of cell therapy went up by 64% over the year compared with 2017.

With relatively new cell therapy companies such as Orchard Therapeutics and Autolus listing on the stock market and reaching over a billion euro market cap, it seems that interest in cell therapies continues to increase.

“We feel like there’s something going on in cell therapy,” emphasized Alessandri. “We have some interest from everywhere in the field – industrial, pharmaceutical companies, biotech.”

Disley believes now is the time to get into cell therapy, which is why he decided to join Mogrify earlier this year. “Just looking at my experience with Mogrify so far, it’s just been off the charts. We’ve not approached anyone. People are just showering us with opportunities.”

Cell therapy - cells in lab

Cell therapy - cells in lab

With only a few therapies actually approved and on the market, cell therapy is still largely at the research and development phase, but this seems set to change as more and more therapies are developed. If the highlighted manufacturing problems can be solved and the overall production process streamlined, then it seems inevitable that prices will come down as a result.

In terms of accessibility, the UK seems to be out in front in Europe, with innovative industry-government partnerships such as the Cell and Gene Therapy Catapult pioneering the steps needed to roll out such complex therapies on a country-wide scale.

“The UK Government listened to what we and others were saying and, as part of the Industrial Strategy Challenge Fund, made £30M [€34M] available. It made money available for the National Health Service because it understood that investment is needed for these products to be able to be supplied in an efficient way,” explained Barry.

While there is still some progress needed for cell therapies to become mainstream, it seems to be a good year for cell therapy investment and for biotechs working in the area. 2019 certainly appears to be the start, if not the end, of cell therapy’s move to the big time.

Images via E. Resko and Shutterstock