The administration of clinical-grade CAR+ T cells into thousands rather than tens to hundreds of recipients a year is a welcome goal to broaden the number of patients that can clinically benefit from this immunotherapy. Increasingly, specialized vendors are emerging to assist with this culturing and processing of genetically modified T cells. However, as the industry gears up to undertake this scale-up, there is a heightened tension between the cultures of innovation and application. Patients, oncologists, investigators and investors desire (immediate) access to the existing CAR+ T-cell therapies. This places a premium on the execution of manufacturing plans and the logistics therein. However, there is recognition that the current approaches to the fabrication of CAR species along with their insertion into propagated T cells and subsets needs to be refined and in some cases redesigned to meet the challenge of overcoming inter- and intra-tumor diversity of TAA expression. This is manifested by the drive to personalize T-cell therapies.
A challenge is to maintain emphasis on new approaches to bioprocessing while at the same time codifying the supply chain of CAR+ T cells. This is where academia and industry may coexist, with the former developing and testing new ideas regarding genetic modification of T cells and the latter scaling to achieve global impact on health care. Such academic and industrial partnerships have recently emerged (for example, University of Pennsylvania with Novartis; Memorial Sloan Kettering Cancer Center and Fred Hutchinson Cancer Research Center with Juno Therapeutics; National Cancer Institute with Kite Pharma; Baylor College of Medicine with Bluebird Bio and Celgene) with other relationships in the works. It remains to be seen whether this coupling will keep the flame of innovation alive given the pressures around commercialization and its attendant needs such as protecting the intellectual property, which can limit timely communications and collaborations. For example, will market forces be sufficient to manufacture T cells for oncology (as well as non-cancerous) diagnosis for which there are few candidate recipients? Will CAR+ T cells be manufactured in centralized facilities operating as stand-alone GMP facilities or will their production be undertaken at diverse locoregional facilities operating with a mandate to individualize the genetically modified product?
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