To go or not to go? Biological logic gating engineered T cells
journal contributionposted on 10.05.2022, 01:37 authored by RC Abbott, HE Hughes-Parry, Misty JenkinsMisty Jenkins
Genetically engineered T cells have been successfully used in the treatment of hematological malignancies, greatly increasing both progression-free and overall survival in patients. However, the outcomes of patients treated with Chimeric Antigen Receptor (CAR) T cells targeting solid tumors have been disappointing. There is an unmet clinical need for therapies which are specifically designed to overcome the challenges associated with solid tumors such as tumor heterogeneity and antigen escape. Genetic engineering employing the use of biological logic gating in T cells is an emerging and cutting-edge field that may address these issues. The advantages of logic gating include localized secretion of anti-tumor proteins into the tumor microenvironment, multi antigen targeting of tumors and a potential increase in safety when targeting tumor antigens which may not be exclusively tumor specific. In this review, we introduce the concept of biological logic gating and how this technology addresses some of the challenges of current CAR T treatment. We outline the types of logic gating circuits and finally discuss the application of this new technology to engineered T cells, in the treatment of cancer.
We thank the following for financial support: Isabella and Marcus Foundation, Robert Connor Dawes Foundation, Cure Brain Cancer Foundation and the Brain Cancer Center and WEHI. MRJ is funded by NHMRC.
JournalJournal for ImmunoTherapy of Cancer
Article NumberARTN e004185
PublisherBMJ Publishing Group
Rights Statement© Author(s) (or their employer(s)) 2022. Re- use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
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Science & TechnologyLife Sciences & BiomedicineOncologyImmunologyimmunotherapyreceptorschimeric antigencytotoxicityimmunologiccell engineeringCHIMERIC ANTIGEN RECEPTORPHASE-1 DOSE-ESCALATIONCANCERSWITCHHETEROGENEITYESCAPESAFETYGLIOBLASTOMARECOGNITIONTOXICITYcytotoxicity, immunologicreceptors, chimeric antigenHumansLogicNeoplasmsReceptors, Antigen, T-CellT-LymphocytesTumor Microenvironment