The state of CAR-T therapy manufacturing

CAR-T cell therapies represent a groundbreaking advancement in the treatment of certain cancers. The U.S. FDA has approved seven CAR-T cell therapies, with approximately 150 more in the pipeline targeting 60 different tumor types. Beyond oncology, cell therapy is gaining traction in treating autoimmune diseases such as systemic lupus erythematosus and diabetes, with emerging interest in cardiovascular applications.

However, for both approved and pipeline therapies to become viable treatment options at scale, manufacturers must overcome several challenges. These include managing costs, enhancing productivity, ensuring scalability, and maintaining safety and efficacy — all of which impact patient access and time-to-market. Additionally, innovators are grappling with skepticism regarding the high cost of these personalized drugs and a general lack of patient education, which can lead to fear and hesitation in opting for cell therapy.

Automation and safety are top-of-mind

Manufacturers are striving to streamline processes to deliver critical therapies to patients more affordably and quickly, while prioritizing safety and efficacy. Although current workflows are effective, there is significant potential to further reduce time-to-market and production costs.

Closing and automating key steps in the cell therapy manufacturing process can minimize manual errors within workflows, which will enhance productivity, lower costs, and, ultimately, optimize safety. Instruments and platforms exist to close and automate early workflow steps such as cell isolation, activation and expansion, as well as downstream processes such as harvesting and fill-finish. But a truly industrialized end-to-end manufacturing workflow that is integrated both physically and digitally is the next step to realize next-gen cell therapies. 

Partnerships across the biotech and academic sectors are catalyzing the integration of workflow automation and process analytical technology (PAT), allowing for real-time monitoring of key process parameters, as well as the ability to identify and adaptively control sources of variability and increase manufacturing consistency. Applying PAT to monitor critical quality attributes can also contribute to improved safety and efficiency, leading to shorter product release time and reduced costs. This will set the stage for a more scalable and sustainable future.

The high cost of manufacturing CAR-T therapies remains a significant barrier to widespread adoption and accessibility. Manufacturers are increasingly using metrics such as dose per year per square foot to measure manufacturing efficiency. These market players are evaluating various platforms, instruments, consumables, manufacturing models and other characteristics to get insights that can help them optimize their current workflows and, eventually, unlock unidentified opportunities to further drive cost down.

Emerging cell types

The landscape of cell therapies is expanding with the introduction of new cell types such as T regulatory cells (T regs) and tumor-infiltrating lymphocytes (TILs). T regs are gaining attention for their ability to modulate immune responses, making them promising for autoimmune diseases and rare conditions. TILs have shown potential in targeting solid tumors.

Recent advancements in natural killer (NK) cell therapy, particularly CAR-NK cells, are focusing on enhancing efficacy and safety, exploring applications in various cancers, including solid tumors, and developing strategies for ‘off-the-shelf’ treatments. Key developments include:

• Refining CAR-NK cell therapy through clinical trials, engineering cells with multiple targets, and combining them with other treatments such as drugs, antibodies, and radiation to optimize potency
• Demonstrating the potential of CAR-NK cells in treating solid tumors, as seen in trials targeting the HER2 antigen in neuroblastoma
• Developing CAR-NK cells from induced pluripotent stem cells (iPSCs), creating an allogeneic source of cells, potentially avoiding graft-versus-host disease
• Utilizing T cell receptors (TCRs) to target intracellular antigens, expanding the range of NK cell applications

Looking forward

By helping address the key challenges of cost, speed and safety, each participant in the cell therapy ecosystem is helping to bring lifesaving therapies to more patients. Emerging cell types are broadening the treatment scope of cell therapy, while automation, PAT and strategic partnerships are addressing manufacturing challenges. Emphasizing the safety of these therapies will improve accessibility and build patient trust, ultimately enhancing the impact of CAR-T cell therapies in the fight against cancer and other diseases.