CAR-T cells are “a generation-defining therapeutic,” according to Paula M. Mendes, PhD, professor of advanced materials and nanotechnology at the U.K.-based University of Birmingham, and her doctoral student Hannah K. Williamson. In therapies based on CAR-T cells, a patient’s T cells are engineered to fight disease, and new applications continue to be tested. As of August 19, clinicaltrials.com included nearly 600 CAR-T trials recruiting patients.
Traditionally, CAR-T cells have been developed to fight blood cancers. Nonetheless, Carl June, MD, the Richard W. Vague Professor in Immunotherapy at the Perelman School of Medicine at the University of Pennsylvania and the pioneer of cancer therapies based on CAR-T cells, and his colleagues reported that “evidence from clinical and preclinical studies underscores the potential of CAR-T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease, and other conditions.”
Manufacturing remains a significant barrier
Despite the success and continuing development of CAR-T cells, Williamson and Mendes pointed out that “manufacture remains a major barrier to meeting increased market demand.” In particular, these experts noted that manufacturing CAR-T cells could be accelerated with the ability to monitor critical quality attributes (CQAs) and critical process parameters (CPPs) during bioprocessing. As Williamson and Mendes showed, CAR-T cytokines might improve CQA and CPP monitoring. This method could track the levels of cytokines used to supplement CAR-T bioprocessing and the ones secreted by the cells.
So, Williamson and Mendes explored the use of biosensors of CAR-T cytokines in cultures like those that are used to expand CAR-T cells. Biosensors—such as ELISA-like fluorescent sensors, a sensor based on surface-enhanced Raman spectroscopy, or electrochemical sensors—could be incorporated into the workflow for manufacturing CAR-T cells. But, the use of such biosensors is not straightforward. As Williamson and Mendes note: “However, for supplemented and secreted cytokines to be viewed as CPPs and CQAs, understanding of their relationship with clinical outcomes needs to be enriched, requiring in-depth investigation.”
If the most informative cytokines can be determined and methods of monitoring them can be incorporated into CAR-T bioprocessing, manufacturing could be optimized with feedback loops. Still, a universal solution would be a long shot. As Williamson and Mendes put it: “It is unlikely that there will be one universal sensing solution for all CAR-T manufacture.”
Instead, these scientists expect that cytokine monitoring would require “an array of targeted platforms using appropriately chosen sensing technologies for specific applications.”
One-and-done is rarely part of bioprocessing’s ecosystem. So, CAR-T manufacturers will continue to deal with some tweaking for most patients, even if cytokine monitoring turns out to be a useful tool.
