Selecting costimulatory domains for chimeric antigen receptors: functional and clinical considerations.,Clinical & Translational Immunology

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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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