Driving CAR T-Cell Therapy From Bench to Bedside


Chimeric antigen receptor (CAR) T cells are being lauded as a “cure” for cancer, but what does it really take to bring this therapy to patients?

Scientists first began to experiment with CAR T cells in the late 1980s, when a trio of researchers genetically engineered T cells to express a chimeric T cell receptor fused with a variable domain of an antibody to redirect their specificity (Gross et al, 1989).

They were the first to suggest the use of chimeric T cell receptors in combating tumours. Years later, in 2011, Carl June and colleagues reported that a chronic lymphocytic leukaemia (CLL) patient treated with autologous anti-CD19 CAR T cells showed a complete response (Porter et al, 2011). This finding fuelled the fire in immuno-oncology research, and CAR T cell immunotherapy has since brought new hope to many patients who are seemingly out of treatment options.

[Read more on how CAR-T is playing a role in the treatment of Chronic Lymphocytic Leukemia (CLL) and other cancers]

On the bench, scientists continue their research to improve the design and efficacy of CAR T cells. Research on target selection, including novel systems that allow CAR T cells to recognize combinations of antigens, will expand the usability of CAR T cells to a broader set of malignant and non-malignant diseases. Meanwhile, improvements on methods to genetically engineer T cells can boost production efficiency and diminish potential undesirable effects such as insertional mutagenesis.

Scientists are also discovering new approaches to enhance in vivo efficacy by combining CAR T cells with other forms of cancer therapy or by changing their delivery method. The translation of some of these research studies may be key in getting CAR T cell therapy closer to being a cure. Read more about recent advances in CAR T cell therapy research.

Taking CAR T cells from bench to bedside presents significant challenges that require careful considerations, including the need for robust quality assessment and product stability. Read more on the processes involved in producing CAR T cells for therapy, from apheresis (collection of donor blood components) collection to delivery and administration, in this free Nature Protocols wallchart on the Production of CAR T Cells.

On the bedside, there are currently hundreds of ongoing clinical trials for CAR T cells. Adoptive CAR T cell therapy has created tremendous excitement among scientists, who are eager to seize the opportunity to make a difference in the lives of patients. Hundreds of research groups are in a race to see who can make it from bench to bedside first.

Novartis and Kite Pharma are among the leaders in the race with phase II clinical trials underway. Despite reports of severe side-effects in patients, the observed >80% remission rates for blood cancers are extremely encouraging.

The sky-high cost of producing CAR T cells, and limitations on the availability and regulatory qualification of reagents can be barriers to making CAR T cell therapy accessible.

Despite the competitive nature of the immunotherapy field, groups are forming partnerships to solve these issues. One example is the collaboration between STEMCELL Technologies and GE Healthcare aiming to develop cGMP-grade T cell therapy isolation, activation and expansion products.

Integrated workflow for the manufacturing of CAR T cells using STEMCELL’s reagents.

The currently available T cell isolation, activation and expansion reagents developed by STEMCELL are designed for cell therapy research applications following the recommendations of USP<1043> on Ancillary Materials, and can also be qualified under an approved clinical trial application. Learn more about ancillary material qualification for cell therapy manufacturing.

Learn more at www.stemcell.com/t-cell-therapy

This is a sponsored article by STEMCELL Technologies.