While the first commercial applications are taking place in Europe, scientists are continuously working to improve the efficacy and safety of CAR T cell therapy, to extend the therapy to other indications, and to find solutions for various challenges. CAR T pioneer Stanley Riddell (USA) said: “CAR T cells are now an established therapeutic in blood cancers, especially in B cell malignancies and myeloma, but we are at the infancy.”
Approaches to improve the efficacy (enhance proliferation and persistence of the CAR T cells) and to reduce toxicities include
- targeting multiple antigens (i.e., multivalent targeting),
- using combinatorial therapy,
- using specific types of T cells or a defined composition of T cells to develop CARs (e.g., TEGs and CIK CAR T cells),
- designing novel CAR constructs (e.g., CATCARs),
- designing novel types of CAR T cells (e.g., TRUCKs, TRAC-CAR T cells).
Approaches to solve challenges such as production speed and costs include
- using novel gene transfer technologies (e.g., PiggyBac and Sleeping Beauty),
- optimizing the manufacturing processes (e.g., point of care manufacturing and ‘off the shelf’ allogeneic therapies).
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