Understanding RBPs in Cancer Immunity
Research type
Research Study
Full title
Understanding RNA Binding Proteins in Cancer Immunity
IRAS ID
354689
Contact name
Martin Turner
Contact email
Sponsor organisation
Babraham Institute
Clinicaltrials.gov Identifier
BB/Y006917/1 , Additional Funder - BBSRC; 226660/Z/22/Z, Additional Funder - Wellcome
Duration of Study in the UK
5 years, 0 months, 2 days
Research summary
Chimeric Antigen Receptor T (CAR-T) cell therapy has been successful in the treatment of blood tumours. However, similar success has not been observed in solid tumours due to the hostile tumour microenvironment and tumour genetic diversity.
One of the main mechanisms by which CAR-T cells get rid of the tumour is by direct lysis of the tumour cells. Therefore, one of the strategies to make more potent CAR-T cells consist in improving their cytotoxicity.
The Turner lab has identified 44 ribonucleic acid (RNA) Binding Proteins (RBPs) as limiting cytokine production independently from a role in proliferation and survival. Amongst the most enriched RBPs were multiple helicases including; Dead-box helicase 6 (DDX6) which mediates the translational suppression of target messenger-RNA (mRNAs) in Processing-bodies, DExH-Box Helicase 30 (DHX30) which is required for mitochondrial ribosome formation, and Dead-box Helicase 28 (DDX28), which has also been associated to mitochondrial ribosome formation as well as cell fitness within low oxygen conditions by interacting with Hypoxia-Inducible Factor 2a. These data implicate helicase RBPs as having a role in T cell function.
In addition, T cells make use of differential splicing of mRNA to facilitate maturation, activation and signal propagation with the use of different splice forms affecting T cell processes such as target sensitivity. The Turner lab is investigating the usage of different mRNA splice sites at different stages of T cells development and activation.
This work will be conducted at the Babraham Research Institute using anonymous, pre-existing blood samples from healthy donors with no selection criteria acquired from the NHS Blood and Transplant Service and a supplier.
These data will be useful to build up the next generation of cell therapy in solid tumours and enhance our understanding of the role of helicase RBPs in T cell maturation and function.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
25/YH/0136
Date of REC Opinion
17 Jul 2025
REC opinion
Favourable Opinion