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Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations.
Clinical & Translational Immunology ( IF 4.6 ) Pub Date : 2019-05-22 , DOI: 10.1002/cti2.1049
Robert Weinkove 1, 2, 3 , Philip George 1, 2 , Nathaniel Dasyam 1 , Alexander D McLellan 4
Affiliation  

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.
更新日期:2019-11-01
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