CAR-T Therapy: Pushing the Boundaries in Cancer Treatment and Biopharma Manufacturing

The success of CAR-T therapies in the fight against cancer has sparked major interest, leading to more than 900 clinical trials.

It’s an exciting — some would say potentially game-changing — time in the fight against cancer.

With the initial success of Chimeric Antigen Receptor T-Cell (CAR-T) therapies from Kite Pharma and Novartis, additional companies are entering the field, with more than 900 clinical trials running currently.

The therapy is not without challenges, with questions about price, manufacturing and patient safety still to be addressed. New advances aim to overcome these challenges, giving the next generation of CAR-T therapies a strong market and exciting future.

CAR-T therapy redefines customized manufacturing.

CAR-T cell therapy is a form of immunotherapy that uses a patient’s T cells — a part of the immune system — to fight cancer. Currently, the FDA has approved the therapy for some forms of non-Hodgkin lymphoma in adults and for patients with advanced lymphoblastic leukemia up to age 25. Development for additional CAR T-cell therapies is underway to target other blood cancers, and researchers are exploring applications for solid tumors as well.

Because the therapy involves collecting blood from a patient, separating T cells from the sample, genetically altering and replicating the T-cells to produce the cancer-fighting CAR receptors, and returning the T-cells to the patient, the process redefines the concept of customized manufacturing.

“In many manufacturing industries, there’s some customization, but you don’t have a truly personalized iPhone that’s designed to fit your hand and body,” Qasim Rafiq, senior lecturer in bioprocessing of regenerative, cellular and gene therapy at University College London, tells Genetic Engineering & Biotechnology News. “Manufacturing individual batches for each patient is true personalization. In a manufacturing sense, it’s truly unique, and manufacturing science is trying to understand how to do it.”

Off-the-Shelf Treatments and Manufacturing Efficiencies May Address Time and Cost. 

The customization required by the existing process impacts two production basics — time and cost. For example, Kite’s Yescarta® takes 17 days on average to manufacture, at a retail price of $373,000.

Efforts are underway to address these challenges, both to improve care — patients having to wait for the 17 days it takes for their cells to be sent to a manufacturing facility, modified and returned — and to create a more viable business model. The most innovative approaches ask, “Can an off-the-shelf product that doesn’t require customized manufacturing replace the current therapies?”

Cellectis has already conducted clinical trials for off-the-shelf treatments using allogeneic CAR-T therapy — sourcing and storing cells from healthy donors in place of engineering cells from individual patients. Celyad has run similar trials with positive results.

In both cases, allogeneic therapy also reduced the more significant side effects associated with the treatment, which include the inflammatory condition called cytokine release syndrome (CRS) and neurologic difficulties.

Other advances include Ziopharm Oncology’s use of DNA plasmids to reduce the time from modification to infusion to two days or less. Companies are also looking to increase manufacturing efficiency by applying best practices in automation.

“We need to learn from the masters of supply chains, such as Amazon,” says Rafiq, “where the customer making a purchase triggers a chain reaction that is — in many instances — completely automated.”

CAR-T’s Future Promises Challenges and Rewards.

CAR-T therapies show much promise for future treatments, but there is a lot we still need to understand.

Trial results have been impressive — with remission rates of up to 94% — especially considering that the patients involved have not responded well to previous treatments. That said, can the treatment’s side effects be minimized? Can process improvements and manufacturing advancements reduce the cost and remove barriers to more wide-ranging applications?

With so many clinical trials underway, these challenges are likely to be met. As Michel Sadelain, a founding director of Memorial Sloan Kettering’s Center for Cell Engineering, told The Scientist, CAR-T is already a game-changer.

“CAR-T therapy is, at the same time, cell therapy, gene therapy, and immunotherapy. It represents a radical departure from all forms of medicine in existence until now.”

Want to know more about CAR-T therapy manufacturing and innovation? Contact Actalent now.