Tim Taga Engineering Project Manager Terumo BCT

Taking CAR T-Cell Therapy from the Lab to the Patient Means Commercializing Where Few Have Succeeded

If you want to get a sense of the excitement level around immunotherapy cancer treatments, look at the frenzy of acquisitions and other large investments pharmaceutical companies are engaged in as they keep up with new developments. You’ll go dizzy trying to stay current. One of the promising therapies involves equipping T cells with chimeric antigen receptors (CARs), which enable them to identify, target and destroy cancer cells. CAR T-cell therapy shows incredible potential, but the companies looking to manufacture these super-soldier cells have some big questions ahead of them.

I watched the beginning of CAR T cell research some twenty years ago, and we seem to be nearing the crescendo from its first breakthrough into applications for patient care. Results from trials testing the efficacy of CAR T cells against blood cancers like leukemia have been positive. Many pharmaceutical companies are in Phase III of their research, almost ready to step into commercialization. However, taking their cells from the lab to the marketplace means scaling up production capability, which isn’t easy.

As companies choose from different devices and processes for possible commercialization, they’re building the bridges between research and the patients they’ll ultimately serve. The tricky part is that there hasn’t been enough time to determine the best ways to build these bridges.

While the healthcare community is still inventing the wheel for commercializing these treatments, there are some pointers that can help guide companies involved in CAR T-cell therapies as they consider their options.


Flexibility

Thinking about flexibility in your CAR T-cell commercialization is thinking about the future of your business. For example, one of the questions facing us is whether cell enrichment or cell purity will prove to be more important when separating cells for this therapy. Some devices offer remarkable purity, while others offer enrichment, and still others offer some of both.

Flexibility is valuable because CAR T-cells may have many more surprises in store for us. There’s work underway to see how well these cancer killers perform against solid tumors, and we may find that using different types of white blood cells can work better to attack different forms of cancer.

Keeping pace with the evolution of cancer immunotherapy is a tall order for companies with rigid, single-purpose manufacturing devices. Of course, anyone working in a lab knows processes need to be consistent so results stay the same. However, it’s good to have devices that are able to adapt to new processes you may start in the future.


Closed, Automated Systems

If you have a closed system for your CAR T-cell manufacturing, you’re ahead of the curve. The difficulty in moving toward process automation stems from the comfort people often have with manual steps, as well as the limited availability of devices that enable closed manufacturing. Especially in this field, where many companies are still in the research phase, moving to a closed system is a dramatic but necessary change to scale up efficiently.

The shift from performing the work by manual means to using automated devices is a fundamental step for the commercialization challenge. Once you’ve finally completed Phase III of your research, it may feel strange to suddenly start looking for closed, automated systems to do much of the work for you.

The manual processes developed during research are often difficult to scale up. It’s a large capital investment, and it would create more demand for people and time than a closed, automated system. Think of it this way: The higher a cleanroom’s classification, the more it will cost, and closed systems may not require the same cleanroom demands as the processes typically used in research phases.


End-to-End Solutions

End-to-end solutions can help for optimum cell therapy practices like cell collection, cell separation, and more. Cell therapy manufacturing poses unique obstacles because key devices and processes don’t always come from the same supplier. There are many device manufacturers in cell therapy, but not many offer a portfolio broad enough to carry CAR T-cell manufacturing processes from beginning to end, especially such processes that include third-party locations like hospitals and vector manufacturing facilities. To work around this dilemma, some companies are mixing and matching devices from different suppliers or using devices in new ways for certain steps in their processes.

With the pace of CAR T-cell developments and the substantial investments needed, it is understandable how tempting it can be to create a manufacturing process with devices from different suppliers, but those devices may not work together as well as if they all came from the same supplier. For example, devices from the same supplier could have data and workflow management enabled with software interconnectivity, which is critical to maintain chain of custody for cell products.

Whatever you choose, end-to-end solutions composed of automated devices at every step are probably going to be used by nearly every CAR T-cell manufacturer in the future. They provide efficiency and productivity in manufacturing for what may become a vital therapy for many patients.

No one knows for certain what new discoveries will shape the future of CAR T-cell therapy. Blood cancers seem to be the most promising, but don’t be surprised if new buzz is created around other applications. Professionals at pharmaceutical companies, medical device manufacturers, cancer centers, and other organizations are pondering the many unanswered questions around cancer immunotherapy. For now, building a flexible, automated, closed, end-to-end manufacturing process with devices that can adapt to new uses will position CAR T-cell manufacturers for present and future success in supplying cancer-fighting cells. 







































Tim Taga is an engineering project manager at Terumo BCT. He led development of the Elutra® Cell Separation System, which can be used in CAR T-cell manufacturing with other Terumo BCT devices. D.J. Martin (dj.martin@terumobct.com), external communications specialist at Terumo BCT, contributed to this article.

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