Browsing by author "Rabbitts, Terence"
Now showing items 1-20 of 28
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A cell-based screening method using an intracellular antibody for discovering small molecules targeting the translocation protein LMO2.
Bery, N; Bataille, CJR; Russell, A; Hayes, A; Raynaud, F; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2021-04-01)Intracellular antibodies are tools that can be used directly for target validation by interfering with properties like protein-protein interactions. An alternative use of intracellular antibodies in drug discovery is ... -
A non-cell autonomous mouse model of CNS haemangioblastoma mediated by mutant KRAS.
Bao, L; Al-Assar, O; Drynan, LF; Arends, MJ; Tyers, P; et al. (NATURE PORTFOLIO, 2017-03-21)Haemangioblastoma is a rare malignancy of the CNS where vascular proliferation causes lesions due to endothelial propagation. We found that conditionally expressing mutant Kras, using Rag1-Cre, gave rise to CNS haemangioblastoma ... -
A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
Bery, N; Miller, A; Rabbitts, T (NATURE PUBLISHING GROUP, 2020-06-26)Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for ... -
An antibody-drug conjugate with intracellular drug release properties showing specific cytotoxicity against CD7-positive cells.
Zhang, J; Jain, A; Milhas, S; Williamson, DJ; Mysliwy, J; et al. (PERGAMON-ELSEVIER SCIENCE LTD, 2021-09-01)Refractory T cell acute leukaemias that no longer respond to treatment would benefit from new modalities that target T cell-specific surface proteins. T cell associated surface proteins (the surfaceome) offer possible ... -
Bioluminescence Resonance Energy Transfer 2 (BRET2)-Based RAS Biosensors to Characterize RAS Inhibitors.
Bery, N; Rabbitts, TH (Wiley, 2019-06-01)Protein-protein interactions (PPIs) are principle biological processes that control normal cell growth, differentiation, and homeostasis but are also crucial in diseases such as malignancy, neuropathy, and infection. Despite ... -
BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.
Bery, N; Cruz-Migoni, A; Bataille, CJ; Quevedo, CE; Tulmin, H; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2018-07-10)The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding ... -
Cancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3.
Chambers, JS; Brend, T; Rabbitts, TH (NATURE PORTFOLIO, 2019-06-12)Many tumour causing proteins, such as those expressed after chromosomal translocations or from point mutations, are intracellular and are not enzymes per se amenable to conventional drug targeting. We previously demonstrated ... -
Cloning, purification and structure determination of the HIV integrase-binding domain of lens epithelium-derived growth factor.
Hannon, C; Cruz-Migoni, A; Platonova, O; Owen, RL; Nettleship, JE; et al. (INT UNION CRYSTALLOGRAPHY, 2018-03-01)Lens epithelium-derived growth factor (LEDGF)/p75 is the dominant binding partner of HIV-1 integrase in human cells. The crystal structure of the HIV integrase-binding domain (IBD) of LEDGF has been determined in the absence ... -
Competitive SPR using an intracellular anti-LMO2 antibody identifies novel LMO2-interacting compounds.
Canning, P; Bataille, C; Bery, N; Milhas, S; Hayes, A; et al. (ELSEVIER, 2021-03-29)The use of intracellular antibodies as templates to derive surrogate compounds is an important objective because intracellular antibodies can be employed initially for target validation in pre-clinical assays and subsequently ... -
Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study.
Hastie, KM; Li, H; Bedinger, D; Schendel, SL; Dennison, SM; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2021-10-22)Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could ... -
Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation.
Barone, C; Orsenigo, R; Cazzola, A; D'Errico, E; Patelli, A; et al. (MDPI, 2023-07-14)Infant acute myeloid leukemia (AML) is a heterogeneous disease, genetically distinct from its adult counterpart. Chromosomal translocations involving the KMT2A gene (MLL) are especially common in affected infants of less ... -
Identification of a minority population of LMO2+ breast cancer cells that integrate into the vasculature and initiate metastasis.
Sikandar, SS; Gulati, GS; Antony, J; Fetter, I; Kuo, AH; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2022-11-11)Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1+/VEGFA+ ... -
Immunopolymer Lipid Nanoparticles for Delivery of Macromolecules to Antigen-Expressing Cells.
Jain, AK; Bataille, CJR; Milhas, S; Miller, A; Zhang, J; et al. (AMER CHEMICAL SOC, 2020-12-21)Macromolecules such as antibodies and antibody fragments have been reported to interfere with intracellular targets, but their use is limited to delivery systems where expression is achieved from vectors such as plasmids ... -
Intracellular antibodies and biodegraders: Beyond small molecules and back again
Cardella, D; Sanchez-Guzman, D; Rabbitts, TH (ELSEVIER, 2023-09-01) -
Intracellular Antibodies for Drug Discovery and as Drugs of the Future.
Rabbitts, TH (MDPI, 2023-03-16)The application of antibodies in cells was first shown in the early 1990s, and subsequently, the field of intracellular antibodies has expanded to encompass antibody fragments and their use in target validation and as ... -
Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.
Bao, L; Hannon, C; Cruz-Mignoni, A; Ptchelkine, D; Sun, M-Y; et al. (NATURE PORTFOLIO, 2017-12-04)Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for ... -
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
Bery, N; Legg, S; Debreczeni, J; Breed, J; Embrey, K; et al. (NATURE PUBLISHING GROUP, 2019-06-13)Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ... -
LINGO-1 is a New Therapy Target and Biomarker for Ewing Sarcoma.
Jain, A; Zhang, J; Rabbitts, T (2017-01-05)Ewing sarcoma is a predominantly paediatric cancer with a high rate of metastasis and reoccurrence. A new surface marker called LINGO-1 was recently identified on Ewing tumours as a potential target for antibody-mediated ... -
Lipid-mRNA Nanoparticle Designed to Enhance Intracellular Delivery Mediated by Shock Waves.
Zhang, J; Shrivastava, S; Cleveland, RO; Rabbitts, TH (AMER CHEMICAL SOC, 2019-03-20)Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs, e.g., recombinant protein, expression plasmids, or mRNA), which is a major barrier for clinical translation of macrodrug-based ... -
LMO2 and IL2RG synergize in thymocytes to mimic the evolution of SCID-X1 gene therapy-associated T-cell leukaemia.
Ruggero, K; Al-Assar, O; Chambers, JS; Codrington, R; Brend, T; et al. (NATURE PUBLISHING GROUP, 2016-09-01)