Automation: ‘The only way to truly scale cell therapy manufacture’ says Lonza

Lonza says it has achieved a significant milestone with partner Sheba Medical treating its first patient with a CD19 CAR-T cell immunotherapy made using the automated point-of-care Cocoon technology.

In March 2019, Swiss CDMO Lonza entered a partnership with Israel’s Sheba Medical Center to provide automated and closed CAR-T manufacturing using its point-of-care (POC) Cocoon cell therapy manufacturing platform.

This week, Sheba and Lonza announced the first patient has been dosed with a CD19 CAR-T cell immunotherapy made using the technology in a phase II cancer trial.

Image: iStock/Duncan_Andison

Sheba’s ongoing immunotherapy program has already treated 100 oncology patients with its CAR-T CD19 therapy with good clinical success. The therapy is currently manufactured at the point-of-care using an open, clinically validated manual process. However, this first patient to be treated with a Cocoon-made CAR-T is significant as it demonstrates the potential of the Lonza’s system in scaling up the manufacture of cell therapies, Eytan Abraham, head of Personalized Medicine at Lonza, said.

“The ultimate goal of this, as well as other cell and gene therapies, is to treat large patient populations,” he told Bioprocess Insider. “The Cocoon platform represents an ideal solution for Sheba, solving the shortage of resources – e.g., manpower, clean room space – and manufacturing bandwidth.”

A further ten patients will be tested with the Cocoon-manufactured CAR-T candidate, he added, before the results are reviewed by the Israeli Ministry of Health.

“Assuming this goes well, the intention is that Sheba transitions to using the Cocoon for all CAR-T manufacturing,” he continued, though noted that with a process change for any candidate being investigated in an ongoing clinical trial Sheba will need to show product comparability and receive approval from the Israeli Ministry of Health.

“A full clinical comparability study confirmed that the product produced in the current manual process is indeed comparable to the product produced in the Cocoon platform.”

Cocoon system

Developed by Octane Biotech, Lonza began working with the system in 2015 to help develop the platform for autologous cell therapy manufacturing. The automated and closed platform is a single system that can be used for a variety of different autologous cell therapy protocols, including CAR-T, but also tumor-infiltrating lymphocytes (TILs) and Mesenchymal stem cells (MSCs).

In October 2018, Lonza acquired an 80% stake in Octane and according to Abraham has significantly advanced the system since.

“The main activities have been improving the system’s robustness and readiness for commercial sale and clinical manufacturing. This included full qualification of the system, passing all regulatory, safety and quality requirements, scaling up manufacturing, obtaining EU CE marking as well as DMF submission to the FDA, and much more.

“Now that the system is launched and proven, we are hard at work, further developing it and enabling additional key capabilities, which will make it even more compelling and efficient. These include capabilities such as adding integrated magnetic cell separation and integrated cell electroporation (using the Lonza Nucleofector system).”

Cost in translation

Autologous CAR-T therapies – such as Novartis’ Kymriah (tisagenlecleucel) and Gilead/Kite’s Yescarta (axicabtagene ciloleucel), both of which have been commercialized – come at a cost. The personalized nature of the therapy gives rise to the adage ‘the product is the process’ which, roughly translated, means scaling up manufacturing is difficult if not impossible and the cost is high.

Thus, “the only way to truly scale cell therapy manufacturing is automation,” said Abraham. “The scalability of cell therapy manufacturing will become be critical as more cell therapies continue to reach late phase clinical trials and are commercialized.”

He continued: “Adding more Cocoon systems will not require much additional footprint thanks to the Cocoon tree, which allows to array multiple cocoons on a central axis. Up to 10 individual processes will be able to be run within approximately 1 m².”

On top of Sheba, other cell therapy developers have therefore turned to Lonza and its Cocoon technology to address this problem. Lonza inked a research collaboration with Stanford University School of Medicine, Fred Hutchinson Cancer Research Center, and Parker Institute for Cancer Immunotherapy earlier this year. And in March, Triumvira Immunologic announced a deal to utilize the Cocoon system, with Triumvira CEO Paul Lammers stating at the time that “it is critical to leverage innovative technology to automate manufacturing processes to improve consistency, accelerate logistics, reduce footprint, and reduce cost.”

Abraham added Lonza is working with other undisclosed partners to place their patient scale cell therapies into the Cocoon system for clinical manufacturing and expects to enter many more Cocoon collaborations – whether with a centralized or decentralized manufacturing model.