30 Years of Pioneering Work for Cell and Gene Therapies
A conversation with Dr. Felicia Rosenthal
Felicia Rosenthal co-founded CellGenix, now Sartorius CellGenix, in the mid-1990s when fewer than 50 gene therapies were in clinical trials. Today, there are 6,000 experimental candidates in development and around 60 approved therapies, many of which benefited from the high-quality growth factors, cytokines, and cell culture media, provided by Felicia and her team. After 30 years of pioneering work, Felicia has stepped away from operational roles and joined the advisory board of Sartorius CellGenix.
For the Sartorius blog, she shares insights about her journey in cell and gene therapies (CGTs), future developments in this area, and Sartorius' role in advancing new therapies.
This article is posted on Sartorius Blog.
Felicia, you founded CellGenix in 1994 as a spin-off of Freiburg University. Take us on a time travel: How did this come to be?
In the early 1990s, I was part of a research group that led one of the first clinical gene therapy trials in the U.S. When we founded CellGenix in 1994 in Freiburg, Germany, there were fewer than 50 clinical gene therapy trials worldwide.
Our ambition was to bring this breakthrough technology to Germany, so we started with gene therapy trials ourselves. At that time, there was hardly any specific regulatory framework for this new type of medical treatment or pharmaceutical manufacturing in Germany. There was also no established formal ways for approving these kinds of drugs. Therefore, a lot of direct interaction with the regulatory agencies was required.
Two years later, together with Schering AG, Berlin, we formed a joint venture to process and manufacture cell therapy products under GMP conditions. To my knowledge, we were the first company in Europe to hold a manufacturing authorization for cell therapies.
Our ambition was to bring this breakthrough technology to Germany, so we started with gene therapy trials ourselves.
Felicia Rosenthal
If someone had told you back then that there would be around 60 approved CGTs worldwide in 2024, would you have been surprised - or disappointed that there aren't more yet?
To be honest, at that point in time, we never thought in terms of numbers.
I was always very confident that cell and gene therapies would eventually succeed medically and commercially. But as with every new technology, there is always a great deal of initial hype with people expecting successes right away. And then the first setbacks come - and this was exactly the case with gene therapies.
For example, there were severe clinical side effects, which slowed down advancements in the field. The larger pharmaceutical companies were hesitant to enter the field, because it was - and still is – a completely new field of medicine, unlike anything else. It was not like producing recombinant protein-based therapeutics, which was still very innovative at that time, and certainly not like a pre-packaged medicine off a pharmacy shelf. It was about bringing living cells or genes into patients.
Therefore, especially the financing part was challenging in the beginning. But as established pharmaceutical players entered the field step by step, we have seen major clinical breakthroughs leading to the first approvals, and so the market for cell and gene therapies has grown.
Looking back at the first product you launched: Does it still exist today?
The first products that we brought to market were cell therapeutic products – medical treatments that use living cells to repair or restore damaged tissue, treat blood diseases or help the immune system find and destroy cancer cells. As mentioned, at this time regulatory agencies did not require approval of these patient-specific products, so we manufactured several different cell therapy products under a GMP manufacturing authorization.
But they are not on the market anymore because we eventually decided to focus on a different type of product: We realized that there were not any high-quality reagents available for cell processing and that there was a market niche. Because we were actually developing and producing optimized cell culture media for our own production already, we were ready to fill that key niche in the market. Our media, as well as recombinant, critical growth factors support the growth and differentiation of various types of cells and are thus essential components for cell and gene therapies.
You could say we switched sides, from being a cell therapy product manufacturer ourselves to becoming a supplier for critical reagents.
Did this manufacturing background help in switching to the supplier side?
Absolutely, this was one of our unique selling points in the beginning because we knew exactly what the customer needed. I am also convinced that having been a producer helps from a regulatory point of view. From the start, we were involved in setting regulatory standards and frameworks. The U.S. Pharmacopeia, a scientific nonprofit organization that sets quality standards in medicine, approached us to help them co-write certain chapters for the industry, and to provide reference standards for cytokines. This shows that not only our customers but also regulatory bodies recognize that we were pioneers and thought leaders in this field.
Sartorius CellGenix has been present in the Cell and Gene Therapies market for thirty years now: How has the market evolved?
In a nutshell: From fewer than 50 to more than 1,800 clinical trials in three decades.
There have been major clinical breakthroughs. In my opinion, the most important one being CAR-T cells, which led to the approval of the first CAR-T cell therapy in 2017 — and quite a few more since then. This was revolutionary!
In a nutshell: From fewer than 50 to more than 1,800 clinical trials in three decades.
Felicia Rosenthal
What has changed as well are new genetic engineering technologies, like the CRISPR technology. The first clinical trial using CRISPR was done in 2019, and already in November 2023, the first product, a treatment against sickle cell disease, was approved. That was incredibly fast, also because the framework and conditions have been adapted to make such quick approvals possible.
By the way, our products — cell culture media and cytokines — are part of the manufacturing process of some of the approved cell and gene therapy products on the market. That is very rewarding and something I am particularly proud of.
Where do you see the market headed? And what developments do you expect for the future?
I am expecting additional technological improvements, in vectors and in cell processing technology, that increase the efficiency of transfection and transduction, making cell processing safer and the process times shorter.
I also expect additional medical success stories. I believe that we will see higher gene expression, and we can expect targeted gene editing with lower off-target effect or hopefully eventually no off-target effects.
We will see targeted in-vivo gene therapeutic approaches, and we will be able to target solid tumors. And then, from solid tumors to non-oncological diseases.
Genetic diseases are already treated with cell and gene therapies as they are ideally suited for gene-modifying technologies because most inherited genetic diseases derive from just one genetic mutation. Therefore, if you can redirect or correct that gene, you can correct that disease.
Most of these diseases are orphan diseases, so not a lot of patients are affected. Still, if we have addressed the harder challenges or broad medical needs, then drugs targeting rare medical conditions, for which there are no therapeutic alternatives today, are a good way to advance the field.
Sartorius has made several strategic acquisitions to build a technology platform for cell and gene therapy applications. How do you see the company positioned in the field?
I believe the company now has everything it needs to offer customers integrated solutions, ranging from reagents and media, to tools, to services, to regulatory support. And I think Sartorius is well-positioned to become a leading supplier for cell and gene therapy manufacturers.
You mentioned setbacks when talking about the first development years of CGTs. How did you personally deal with lowlights in your career?
I always try to focus on the goal. As a scientist, you are used to setbacks or having to repeat an experiment to achieve a certain result. And I always gave my best and hoped to achieve my goal eventually.
Fortunately, I find it easy to motivate myself. As a physician, my core drive has always been to help patients. This has guided everything I did when developing or working on a product.
I am thankful if I can make at least a small contribution to advancing medicine, and I think that as a company, we have already made important contributions to this goal.
After your retirement, you are still part of the advisory board of Sartorius CellGenix. Is there a particular milestone that you would like to see Sartorius CellGenix reach?
First of all, I am really grateful that Sartorius offered me the opportunity to stay on the advisory board, where I can share my insights and perspectives and stay informed about ongoing developments.
Regarding the milestones, I am very much looking forward to the launch of a new animal component-free cell culture medium for T cells, which we have been working on for several years. Another bigger milestone is the completion and inauguration of our new building here in Freiburg.
And finally, I am very excited to see how the company is integrating all the acquired businesses, enabling Sartorius to offer customers a complete range of technologies for the development and production of CGTs.
