The authors review the opportunities and challenges presented by universal allogeneic CAR T-cell therapies.
One of the most promising approaches in cancer treatment is chimeric antigen receptor (CAR) T-cell therapy, in which part of the body's own immunological defendors, T-cells, are redirected against cancerous cells after being engineered to express CARs. Since their initial development in the early 90s, CAR T-cells have evolved through several generations. The use of autologous (patient-derived) CAR T-cells has proven to be successful in treating people with certain blood cancers such as B-cell malignancies. However, autologous CAR T-cell therapy is not suitable for all patients, and it often requires a long and expensive manufacturing process since each treatment must be made individually for each patient.
'We realized early on that refined gene-editing techniques were what was needed to take an allogeneic approach to CAR T-cell therapy,' said Dr.
One of the major challenges in the allogeneic approach involves mitigating the risk of graft-versus-host-disease (GvHD) - a medical complication that can present itself in people that have received tissues or cells from another person. The review examines aspects of this challenge and helps weigh the pros and cons associated with the different methods used to create allogeneic CAR T-cells. It also outlines some of the gene-editing work that
'Our immune system, including our T-cells, is incredibly sophisticated. We know that T-cells can now be retasked to successfully fight cancer. There are amazing approaches to gene editing that are driving progress towards the most safe and efficacious versions of allogeneic products. It is exciting to see these approaches applied to 'off the shelf' CAR T-cell products,' said Prof.
Off-the-shelf' allogeneic CAR T cells: new development and current challenges
Stephane Depil1, Philippe Duchateau2, Stephan Grupp3, Ghulam Mufti4, Laurent Poirot2
Formerly
Children's Hospital of
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