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Open AccessReview

The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells

1
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
2
Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
3
Institute of Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 204; https://doi.org/10.3390/ijms21010204
Received: 28 November 2019 / Revised: 23 December 2019 / Accepted: 24 December 2019 / Published: 27 December 2019
(This article belongs to the Special Issue CAR-T Cell Therapy)
The clinical success of chimeric antigen receptor (CAR) T cell immunotherapy in the treatment of haematological cancers has encouraged the extensive development of CAR design to improve their function and increase their applicability. Advancements in protein engineering have seen modifications to both the ecto- and endo-domains of the CAR, with recent designs targeting multiple antigens and including inducible elements. These developments are likely to play an important role in inducing effective CAR T cell responses in a solid tumour context, where clinical responses have not been effective to date. This review highlights the spectrum of novel strategies being employed in CAR design, including for example variations in targeting tumour antigens by utilising different ectodomain designs such as dual chain CARs, natural receptor or ligand-based CARs, and T cell receptor fusion constructs, and also reviews some of the innovative approaches to a “universal” CAR and various multi-antigen targeting CAR strategies. We also explore how choices in the endodomain impact CAR function and how these need to be considered in the overall CAR design. View Full-Text
Keywords: immunotherapy; chimeric antigen receptor T cells (CAR T cells); affinity tuning; dual chain CAR T cells (dcCAR); ligand-based CAR T cells; T cell receptor fusion constructs (TRuCs); universal immune receptors (UIR); dual CAR T cells; tandem CARs (tanCARs); bispecific T cell engagers (BiTEs) immunotherapy; chimeric antigen receptor T cells (CAR T cells); affinity tuning; dual chain CAR T cells (dcCAR); ligand-based CAR T cells; T cell receptor fusion constructs (TRuCs); universal immune receptors (UIR); dual CAR T cells; tandem CARs (tanCARs); bispecific T cell engagers (BiTEs)
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MDPI and ACS Style

Hughes-Parry, H.E.; Cross, R.S.; Jenkins, M.R. The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells. Int. J. Mol. Sci. 2020, 21, 204. https://doi.org/10.3390/ijms21010204

AMA Style

Hughes-Parry HE, Cross RS, Jenkins MR. The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells. International Journal of Molecular Sciences. 2020; 21(1):204. https://doi.org/10.3390/ijms21010204

Chicago/Turabian Style

Hughes-Parry, Hannah E.; Cross, Ryan S.; Jenkins, Misty R. 2020. "The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells" Int. J. Mol. Sci. 21, no. 1: 204. https://doi.org/10.3390/ijms21010204

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