CAR-T cell therapy – novel therapy with great potential

The term “CAR-T” seems to be omnipresent in today’s pharmaceutical and medical fields.  Experts put high hopes on this emerging procedure and have already claimed first successes. But what exactly is the secret hiding behind this four-letter acronym? How does it work, what are its projected chances and are there challenges or risks?


The so-called CAR-T cell therapy is a promising personalized therapy approach in the treatment of patients suffering from acute or chronic leukemia. What may sound like a relatively straightforward procedure, in reality requires complex – and costly – processes that are, however, worth both time and money, as they have massive potential to be used in a broader spectrum.

Experts are hoping to develop treatments that go beyond curing patients suffering from certain types of leukemia and to push the treatment of several tumor diseases to a new level.

Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua.

Thomas Wurm

How blood cells are used
to successfully generate active agents

After all, in this industry safety and secure transportation are fundamental.

Single Use Support’s CGT.STREAM addresses all the above mentioned pain points and facilitates the safe and reliable shipping of buffer salts, primary cells and media.

It covers all the vital steps of the biopharmaceutical logistics process and since it is entirely based on single-use components it is highly flexible and scalable.

Researchers have been busy studying and exploring the CAR-T cell therapy’s potential since the late 1980s. T-Cells are white blood cells that play an important role in the immune system.

For a successful treatment, they need to be extracted from the patient’s blood by means of a blood filtration process before being sent to the lab for further processing.

At the lab, the cells are genetically manipulated in order to generate specific receptors called Chimeric Antigen Receptors​1​ or CARS, which are able to recognize and attack cancer cells. In a process that can take up to four weeks, the cells are then multiplied (genetically engineered T-Cells) so they can be reinjected into the patient’s circulatory system.

Currently, the CAR-T cell therapy is successfully applied in the treatment of leukemia and lymph node cancer.

Prior to this treatment, the patient will undergo chemotherapy, with the aim to destroy as many T-Cells as possible and facilitate the spread of the manipulated CAR-T cells.

Delays and biocontamination can invalidate an entire batch – with massive financial and severe human consequences.

However, medical and pharmaceutical scientists are busy researching new fields of application.​2​ As opposed to already approved compounds, the development of new therapies mostly requires insignificantly small volumes of drug substances.

Nonetheless, these have to be stored and shipped carefully. Diligent handling is imperative, and the sensitive matter does not allow for any glitches – neither during the production process in the lab nor on the final product’s way to the patient.

The CAR-T cell therapy and its success story

Successful treatment of Chronic Lymphocytic Leukemia and Acute Lymphoblastic Leukemia

In 2010, the new therapy was successfully applied for the first time: It is scientifically proven that two patients suffering from chronic lymphocytic leukemia (CLL) could be cured.

And in 2012, a girl suffering from Acute Lymphoblastic Leukemia (ALL) was treated successfully in the US. While the patient, who was 7 years at the time of treatment, reacted with severe side effects, today she is considered to be cured.

In the US and the European Union, there are currently five severe illnesses that can be treated with the CAR-T cell therapy. 300 further applications – more than 100 of which are aimed at various tumor diseases – are being developed at present.

In Germany, the University Hospital Würzburg is a pioneering institution with regards to CAR-T therapies and the experts there have been treating patients with FDA approved CAR-T cell products since 2016.

(Video Source: Youtube, Dana-Farber Cancer Institute – CAR T-Cell Therapy: How Does It Work?)

Further potential fields of application

Apart from the treatment, the institution also focuses on researching further fields of application of this specific personalized therapy, and in 2018, two myeloma patients could be treated successfully. Current findings show that the CAR-T cells remain in the circulatory system even after the tumor cells have disappeared and it is believed that they can attack again in case of a relapse.

Clinical trials use CAR-T cell constructs to research further oncological application options. The cells required for the studies are usually modified at the study centers’ labs before being tested on patients who are not eligible for commercially approved CAR-T therapies, either because of their symptoms or other circumstances.

This development is just one of the signs of the changes that the medical and pharmaceutical world are subjected to. Instead of producing blockbusters in vast quantities, the current trend goes towards producing small volumes of personalized agents on the basis of mutated cells.

And those can easily be generated in a small lab instead of a giant pharmaceutical plant. The changing requirements regarding volumes and procedures bring with it the need for new and innovative processes that are, above all, flexible and agile. The integration of single use technology is one of them.

Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua.

Johannes Kirchmair
CAR-T cell therapy

CAR-T cell therapy – novel therapy with great potential

+
Car-T cell therapy

General chances and challenges of a personalized therapy approach – CAR-T cell therapy

+
CAR-T a promising Theraphy

CAR-T: A promising therapy and its challenges

+

What are the hurdles and challenges regarding CAR-T therapy?

A reliable and sterile logistics process, which includes storage and shipping, is fundamental for the CAR-T cell therapy’s success. We offer the solutions.

Thomas Wurm

Where SUSupport comes into play

In order to not jeopardize the CAR-T cell therapy’s success, an absolutely reliable and sterile logistics process with automated steps is crucial – including for storage and shipping. 

SUSupport, with its headquarters in the Tyrolean Alps, has set itself the goal to address the potential bottlenecks of the pharmaceutical logistics process and to offer solutions that are scalable, so they can be adapted to the actual need.

Side effects of CAR-T therapy

Clinical trials have shown that up to 90 % of patients suffering from B-Cell Leukemia displayed a positive reaction to the CAR-T cell therapy.​3​ At the same time, some patients developed severe side effects, predominantly infectious symptoms (Cytokine Release Syndrome) as well as neurological side effects with at times fatal consequences.

As with many other treatments, the CAR-T therapy’s success always depends on the respective patient’s reaction – in this case to the infusion of his own, mutated, cells. But of course there are also external factors at play that can impact the therapy positively.

Sensitivity

The cells required are not only valuable but also highly sensitive. The personalized therapy is a tedious process that involves the repeated reliable and protected handling of small volumes of valuable substances. Furthermore, the extraction, manipulation and infusion of miniscule volumes are costly procedures.

Any mishaps during this phase – or contamination of the finalized compound – can have dire consequences, both financially and feasibly. This leads to the logical conclusion that mistakes, oversights and losses caused by contamination should not only be ruled out from the beginning; they should be all but avoided.

Costs

As the therapy needs to be tailored to each patient receiving CAR-T cells, it requires elaborate and costly procedures. The industry reacts to the challenges posed by the new approach by developing innovative processes and flexible systems, with the aim to not only make an ancient medical dream come true but also accessible for a wide range of patients.

So far, the CAR-T cell therapy is a complex procedure with exorbitant costs of approximately EUR 275,000 (USD 312,500) per patient – before treatment costs. However, medical experts have high hopes and they see personalized treatment options as nothing less than a quantum leap forward in cancer treatment.

What are the potential risks of the CAR-T cell therapy?

As mentioned before, the chances for success are cause for hope – after all, the majority of patients treated remains cancer free after two years. However, due to the CAR-T cell therapy’s relative “youth”, its lasting effects are not yet extensively researched nor are they proven. There is just not enough scientific data to rely on for long-term prognoses.

We see chances where others might see challenges.

Thomas Wurm

Individual risks

The patient’s blood is extracted and infused via the veins in order to keep the risk of infections as well as physical stress during transplantation at a minimum.

Yet, the patient’s system has been weakened by the preceding chemotherapy, while the CAR-T cell infusion can lead to a number of side effects, which can differ in both impact and severity for each patient.

There is furthermore a risk that the cells cannot be multiplied at the lab or that they do not show the desired effect.

Red tape

As is a standard with any approved medication, Germany – and with it most other European countries – is calling for a measured introduction to the standard care system that postulates thorough and comprehensive evaluation regarding the therapy’s proven benefits.

In order to regulate prices for new medications, there is a call for new and complex cell therapies to be researched and developed not only by established big market players but also by independent labs, which in itself could be a chance rather than a risk.

This would mean that in future labs can produce their own compounds beyond the phase of research and development. And this is where SUSupport’s scalable and agile systems based on single-use compounds come into play.

What is the solution to make CAR-T cell therapy affordable & easily obtainable?

Therapies and medications should not be a luxury but a commodity that – in an ideal world – is available to every person in need. As a commodity it must therefore be affordable and easily obtainable.

In order to guarantee the cells’ safety and sterility as well as assure the affordability of research and development, innovative approaches and solutions are required.

So far, the established systems, including those for freeze-thaw processes, are usually designed for vast amounts of drug substance.

Drug substances that are still in the research or clinical trial phase are neglected. But this is about to change:

With the CGT.STREAM, SUSupport has developed a platform that is scalable and geared towards labs where the handled volumes are usually as little as 0.03 to 0.2 fl oz.

The solution

The system neither requires complicated adaptations nor extensions that might prove difficult to implement in a sterile setting and when time is of the essence – in this way taking affordability and obtainability a step further and tackling these main issues at their roots.

Johannes Kirchmair

Efficacy and scalability with one proven system

A monitored freeze-thaw process assures an optimal product stability so that the high-quality liquids do not lose any of their efficacy when frozen. In order to also protect the valuable drug substances during shipping, they are sent on their way in the RoSS shell, a protective container:

The filled and frozen single use bags are embedded in 3D foam to absorb external impacts and shocks, while a tamper-proof sleeve made of stainless steel offers additional stability and protection.

This combination protects the sensitive single use bags from potential damages that can, in the worst case, cause the contamination of an entire batch and lead to dire consequences. The platform is easy to adapt and allows for the controlled filling as well as the monitored cultivation of cells of any quantity and volume.

Is it possible to treat a wide range of patients?

About half of the patients treated so far were cured, which in medical terms means that two years after treatment they are still without relapse and free of cancer cells. Clinical studies have proven that up to 92 % of treated patients suffering from Acute Lymphatic Leukemia (ALL) could be fully cured. Current findings show that the therapy is particularly effective in the treatment of lymph node cancer and leukemia, as has been highlighted by a global study with more than 1,000 patients.

Currently, only patients suffering from specific types of cancer (blood cancer), and those who did not respond to traditional chemotherapy and stem cell transplants, are being treated. But scientists are – as should be their nature – hopeful. Extensive cancer research regarding the CAR-T cell therapy’s future potential is underway, with a focus on finding new fields of application.

CGT.STREAM - Frozen liquids need to be transported from A to B... we enable it!
CAR-T: Promising therapy with lots of potential - but there are still hurdles to take!

Logistics solution

With the medical and pharmaceutical industries not knowing any standstill, the components- and supplier industries are constantly challenged to provide new solutions.

Any new inventions and developments have to adhere to international standards – or, ideally, they could turn out to be setting new international standards themselves. 

Challenges are the root of any invention; they lie at the heart of every success story. A dedicated team, experience and expertise paired with the will to tackle certain obstacles and to come up with answers that can lead to viable solutions are the determining factors for success.

SUSupport is living proof of this theory. While the young company has already come up with some game-changing developments, they keep pushing the limits of what’s possible, thus remaining true to their role as trailblazers in biopharma logistics industry.

CAR-T cell therapy & gene therapy success story

Seed Train Intensification Process by Single Use Support

Do you know about our innovative seed train intensification process already? We developed a new process, called SEED.Stream – Check it out!

Scientific research

  1. 1.
    Sadelain M, Brentjens R, Rivière I. The Basic Principles of Chimeric Antigen Receptor Design. Cancer Discovery. Published online April 2013:388-398. doi:10.1158/2159-8290.cd-12-0548
  2. 2.
    Skorka K, Ostapinska K, Malesa A, Giannopoulos K. The Application of CAR-T Cells in Haematological Malignancies. Arch Immunol Ther Exp. Published online November 6, 2020. doi:10.1007/s00005-020-00599-x
  3. 3.
    Halim L, Maher J. CAR T-cell immunotherapy of B-cell malignancy: the story so far. Therapeutic Advances in Vaccines and Immunotherapy. Published online January 2020:251513552092716. doi:10.1177/2515135520927164