2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
January 21st, 2025
Version: 1
Department of Inflammation Biology, School of Immunology & Microbial Sciences, Kings College London
cancer biology
biorxiv

GLUT5 armouring enhances adoptive T cell therapy anti-tumour activity under glucose-limiting conditions

Page, R.Open in Google Scholar•Martinez, O.Open in Google Scholar•Larcombe-Young, D.Open in Google Scholar•Bugallo-Blanco, E.Open in Google Scholar•Papa, S.Open in Google Scholar•Perucha, E.Open in Google Scholar

Cancer immunotherapy with engineered T cells has become a standard treatment for certain hematologic cancers. However, clinical trial outcomes for solid tumours are significantly lagging. A primary challenge in solid tumours is the lack of essential metabolites in the tumour microenvironment, such as glucose, due to poor vascularization and competition with tumour cells. To address this, we modified T cells to use fructose as an alternative energy source by introducing ectopic GLUT5 expression. We show that \'GLUT5-armored\' T cells, engineered with either chimeric antigen receptors (CARs) or an ectopic T cell receptor (TCR), achieve enhanced anti-tumour activity in low-glucose environments in both in vitro and in vivo models. This straightforward modification is compatible with current clinical approaches and may improve the efficacy of T cell therapies for solid tumours.

Similar Papers

biorxiv
Wed Jan 22 2025
PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP
Proteasome activator 28{gamma} (PA28{gamma}) plays a critical role in malignant progression of various tumors, however, its role and regulation are not well understood. Here, using oral squamous cell carcinoma (OSCC) as main research model, we discovered that PA28{gamma} interacted with complement 1q binding protein (C1QBP), which is dependent on the N-terminus of C1QBP rather than the known funct...
Wang, J.
•
Shi, Y.
•
Wang, Y.
•
Shen, Y.
...•
Chen, Q.
biorxiv
Wed Jan 22 2025
Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis
Mutations in somatic cells are inflicted by both extrinsic and intrinsic sources and contribute over time to cancer. Tobacco smoke contains chemical carcinogens that have been causatively implicated with cancers of the lung and head & neck. APOBEC family DNA cytosine deaminases have emerged as endogenous sources of mutation in cancer, with hallmark mutational signatures (SBS2/SBS13) that often co-...
Durfee, C.
•
Bergstrom, E. N.
•
Diaz-Gay, M.
•
Zhou, Y.
...•
Harris, R.
biorxiv
Wed Jan 22 2025
Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities
Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperprol...
Zhao, H.
•
Park, Y. M.
•
Zheng, Y.
•
Mao, Q.
...•
Lin, D.-C.
biorxiv
Wed Jan 22 2025
Enhanced AkaLuc Bioluminescence Imaging for Longitudinal Intravital Monitoring of Minimal Residual Disease in a Murine Model of Triple-negative Breast Cancer
Triple-negative breast cancer (TNBC) is an aggressive form of cancer with poor prognosis. Beyond the absence of targeted therapies, a major challenge is its high recurrence rate, driven by the outgrowth of residual tumor cells that survive chemotherapy and persist during minimal residual disease (MRD). To monitor the therapy response of TNBC by enhanced intravital imaging, we established a clinica...
Steinbauer, S.
•
Cowles, J. D.
•
Sabbaghi, M. A.
•
Poppelaars, M.
...•
Csiszar, A.
biorxiv
Wed Jan 22 2025
Isolation and Bioassay of Linear Veraguamides from a Marine Cyanobacterium (Okeania sp.)
Marine cyanobacteria have gained momentum in recent years as a source of novel bioactive small molecules. This paper describes the structure elucidation and pharmacological evaluation of two new, veraguamide O (1) and veraguamide P (2), and one known, veraguamide C(3), analogs isolated from a cyanobacterial collection made in the Las Perlas Archipelago of Panama. We hypothesized that these compoun...
Parker, S.-A. J.
•
Hough, A.
•
Lax, N.
•
Wright, T.
...•
Tidgewell, K. J.
biorxiv
Wed Jan 22 2025
When neighbours play a role: a systems-level analysis of protein interactions conditioning cancer driver mutation effects
Background: Cancer is driven by the accumulation of somatic mutations, including driver mutations that confer a selective advantage to cancer cells. Driver proteins operate within complex interaction networks, and their activity is conditioned by neighbour proteins. Understanding the interplay between driver mutations and the expression of their neighbour proteins can provide insights into cancer ...
Vital, M. F.
•
Miranda, J. A.
•
Carrolo, M.
•
Quintela, A.
•
Pinto, F. R.
biorxiv
Wed Jan 22 2025
PI3K regulates TAZ/YAP and mTORC1 axes that can be synergistically targeted
Purpose: Sarcomas are a heterogeneous group of cancers with few shared therapeutic targets. PI3K signaling is activated in various subsets of sarcomas, representing a shared oncogenic signaling pathway. Oncogenic PI3K signaling has been challenging to target therapeutically. An integrated view of PI3K and Hippo pathway signaling is examined to determine if this could be leveraged therapeutically. ...
Garcia, K. C.
•
Khan, A. A.
•
Ghosh, K.
•
Sinha, S.
...•
Tanas, M. R.
biorxiv
Wed Jan 22 2025
Neoplastic immune mimicry is a generalizable phenomenon in breast cancer and epithelial CD69 enables early tumor progression
Dedifferentiation programs are commonly enacted during breast cancer progression to enable novel cellular phenotypes. Increased cellular plasticity within the neoplastic compartment of tumors correlates with disease aggressiveness, often culminating in greater resistance to cytotoxic therapies or the augmented ability to metastasize to distant organs. Here we report that subpopulations of dediffer...
Berens, E. B.
•
Khou, S.
•
Huang, E.
•
Hoffman, A.
...•
Coussens, L. M.
biorxiv
Wed Jan 22 2025
A bright synthetic near-infrared luciferin enhances the capabilities of deep-tissue bioluminescence imaging using firefly luciferases
Synthetic bioluminescence reactions exhibiting near-infrared (NIR)-shifted spectra have been explored to improve deep-tissue imaging through the design of firefly luciferin analogues. Although the NIR bioluminescence reactions improve the tissue penetration of bioluminescence signals from deep tissues, their photon output is markedly lower compared to the natural reaction with D-luciferin and fire...
Saito-Moriya, R.
•
Iwano, S.
•
Kitada, N.
•
Yamasaki, N.
...•
Kuchimaru, T.
biorxiv
Wed Jan 22 2025
SCAN-ACT: Adoptive T Cell Therapy Target Discovery Through Single-Cell Transcriptomics
The FDA approval of T cell receptor-engineered T cells (TCR-T) for synovial sarcoma demonstrates the potential for adoptive T cell therapies (ACTs) in solid tumors. However, the paucity of tumor-specific targets without expression in normal tissues remains a major bottleneck, especially in rare cancer subtypes. Here, we present a comprehensive computational pipeline called SCAN-ACT that leverages ...
Testa, S.
•
Pal, A.
•
Subramanian, A.
•
Varma, S.
...•
Moding, E. J.