Journal
IMMUNOTHERAPY
Volume 7, Issue 5, Pages 487-497Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/IMT.14.123
Keywords
adoptive cell therapy; CAR T cells; cytokine storm; preclinical models; toxicity
Categories
Funding
- Leukaemia and Lymphoma Research
- Kay Kendall Leukaemia Fund
- Medical Research Council
- Children with Cancer
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Chimeric antigen receptor (CAR) T-cells form part of a broad wave of immunotherapies that are showing promise in early phase cancer clinical trials. This clinical delivery has been based upon preclinical efficacy testing that confirmed the proof of principle of the therapy. However, CAR T-cell therapy does not exist alone as T-cells are generally given in combination with patient preconditioning, most commonly in the form of chemotherapy, and may also include systemic cytokine support, both of which are associated with toxicity. Consequently, complete CAR T-cell therapy includes elements where the toxicity profile is well known, but also includes the CAR T cell itself, for which toxicity profiles are largely unknown. With recent reports of adverse events associated with CAR T-cell therapy, there is now concern that current preclinical models may not be fit for purpose with respect to CAR T-cell toxicity profiling. Here, we explore the preclinical models used to validate CAR T-cell function and examine their potential to predict CAR T-cell driven toxicities for the future.
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