The evolving protein engineering in the design of chimeric antigen receptor T cells
Details
Publication Year 2019-12-27,Volume 21,Issue #1,Page e204
Journal Title
International Journal of Molecular Science
Publication Type
Journal Article
Abstract
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.
Publisher
MDPI
Research Division(s)
Immunology
PubMed ID
31892219
Open Access at Publisher's Site
https://doi.org/10.3390/ijms21010204
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-01-21 11:05:24
Last Modified: 2020-02-10 05:03:04
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