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 sounds like a relatively straightforward procedure, 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. Find out more about the CAR therapy and its related chances and risks in this article.
(Video Source: Youtube, Dana-Farber Cancer Institute – CAR T-Cell Therapy: How Does It Work?)
Researchers have been busy studying and exploring the potential of the CAR-T cell therapy 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 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. 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.
Currently, the CAR-T cell therapy is successfully applied in the treatment of leukemia and lymph node cancer. However, medical and pharmaceutical scientists are busy researching new fields of application. 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. Delays and biocontamination can invalidate an entire batch – with massive financial and severe human consequences. After all, in this industry safety and secure transportation are fundamental.
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.
Currently, in the US and the European Union, five severe illnesses can be treated with the CAR-T cell therapy. 300 further applications – more than 100 of which are aimed against 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.
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 in cancer center 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 with 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 change 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.
In this personalized therapy, the respective patient’s immune cells, the so-called T-cells, are extracted. Those cells are responsible for your body’s immune response system. In their natural state they will not recognize cancer cells, which is why they have to be genetically modified before being reintroduced in the patient’s bloodstream in order to identify diseased or damaged cells and to destroy them. This is made possible by the antigen specific receptors the cells have developed during their processing at the lab.
This type of tumor treatment is nothing short of realizing an ancient dream: It works by using the patient’s own immune system – albeit technologically manipulated – to combat a deadly disease.
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 make the medical dream come true and accessible for a wide range of patients.
About half of the patients treated so far could be 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.
Extensive cancer research regarding the CAR-T cell therapy’s future potential is underway, with a focus on finding new fields of application. Currently, only patients suffering from specific types of cancer (blood cancer), and who did not respond to traditional chemotherapy and stem cell transplants, are being treated.
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 this personalized treatment options as nothing less than a quantum leap forward in cancer treatment.
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. The Austrian company 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.
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.
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. However, 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.
Germany 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.
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.
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. 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.
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.
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: SUSupport has developed with the CGT.STREAM a platform that is scalable and geared towards use in labs where the handled volumes are usually as little as 0.03 to 0.2 fl oz. 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. Quite on the contrary, the platform is easy to adapt and allows for the controlled filling as well as the monitored cultivation of cells.
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.