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Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations
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Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations
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Journal Article
Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations
2019
Overview
Costimulatory signals are required to achieve robust chimeric antigen receptor (CAR) T cell expansion, function, persistence and antitumor activity. These can be provided by incorporating intracellular signalling domains from one or more T cell costimulatory molecules, such as CD28 or 4‐1BB, into the CAR. The selection and positioning of costimulatory domains within a CAR construct influence CAR T cell function and fate, and clinical experience of autologous anti‐CD19 CAR T cell therapies suggests that costimulatory domains have differential impacts on CAR T cell kinetics, cytotoxic function and potentially safety profile. The clinical impacts of combining costimulatory domains and of alternative costimulatory domains are not yet clearly established, and may be construct‐ and disease‐specific. The aim of this review is to summarise the function and effect of established and emerging costimulatory domains and their combinations within CAR T cells.
This review summarises the use of distinct chimeric antigen receptor (CAR) costimulator domains in cancer immunotherapy. We outline the individual characteristics of costimulator domains in CAR T cell function in preclinical and clinical studies.
