CAR T-cell therapy may be on the verge of becoming the standard of care for a few clinical indications. Yet, many challenges pertaining to manufacturing standardization and product characterization remain to be overcome in order to achieve broad usage and eventual commercialization of this therapeutic modality.
Adoptive cell therapy using naturally occurring endogenous tumor-infiltrating lymphocytes or T-cells genetically engineered to express either T-cell receptors or chimeric antigen receptors (CAR) have emerged as promising cancer immunotherapy strategies. Adoptive cell therapy using CD19-targeted CAR T-cells has resulted in remarkable responses in patients with acute lymphoblastic leukemia. Promising clinical outcomes in phases 1 and 2 clinical trial studies have triggered active support and investment from pharmaceutical and biotechnology companies. The manufacturing of clinical-grade CAR T-cells under current good manufacturing procedure (cGMP) is a critical step, and in its current state a bottleneck for the wide implementation of this promising therapeutic modality.
Adoptive cellular therapy involves the ex vivo enrichment and expansion of T lymphocytes. For therapies using T-cells expressing transduced CARs or T-cell receptors, cGMP grade ancillary genetic modification reagents, such as retroviral and lentiviral vectors, are also required. One of the challenges of this largely personalized medicine is the development of efficient technologies and cost-effective clinical manufacturing platforms to support the later clinical trial phases and ultimately commercialization.
CAR T-cells have been shown to be one of the most promising therapeutic modalities for treatment of refractory hematologic malignancies. The design of CARs has evolved drastically over the years. Features, such as the coexpression of costimulatory molecules, cytokines, and suicide genes are incorporated to further improve efficacy and safety. The tumor targets for CAR T-cells have expanded from CD19 to a multitude of new targets. Adoptive CAR T-cell therapy will hopefully prove to be as effective in solid tumors as in onco-hematological indications.
The initiation of manufacturing, with defined subpopulations of T-cells that can be derived from a blood draw instead of a leukapheresis product, would reduce the scale and therefore the cost of manufacturing. New sources of T-cells that could alleviate the need to obtain autologous T-cells are also being investigated.
The intensified interest from biotech and pharmaceutical companies will surely accelerate the development of improved manufacturing platforms. An increasing number of tools are available for clinical CAR T-cell manufacturing and consortiums, such as the CCRM and NNMI are forming.
The optimization of appropriate quality control release testing and tracking of products will need to be drastically improved in terms of efficiency and cost effectiveness. The simplification of workflows, the increase in process robustness, and the implementation of automated closed systems should enable scalability and reduce the cost of goods, while maintaining the efficiency of the CAR T-cell products. The participation and cooperation between the various stakeholders should accelerate the path to commercialization.
For more information on CAR T-Cells, join me at Cell & Gene Therapy Bioprocessing & Commercialization event this October in Boston. And for special savings, be sure to use the VIP code “B16188BLOG” – See you this October.
About the author: Justin Gaines is a Boston-based drug discovery professional and biotech enthusiast. During his tenures he has remained active within the biomedical engineering and regenerative medicine sectors, and has remained an avid proponent of bringing together the Boston life science community. He is currently leading the Bio Pharma Networking Group across the North East – a professional life science and healthcare community spanning 6K members. View his last contribution to KNect365 Bioprocessing here.