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dc.contributor.authorChambers, JSen_US
dc.contributor.authorBrend, Ten_US
dc.contributor.authorRabbitts, THen_US
dc.date.accessioned2020-03-04T16:37:29Z
dc.date.issued2019-06-12en_US
dc.identifier.citationScientific reports, 2019, 9 (1), pp. 8553 - ?en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3533
dc.identifier.eissn2045-2322en_US
dc.identifier.doi10.1038/s41598-019-44908-7en_US
dc.description.abstractMany 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 an approach (Antibody-antigen Interaction Dependent Apoptosis (AIDA)) whereby a single anti-β-galactosidase intracellular single chain Fv antibody fragment, fused to inactive procaspase-3, induced auto-activation of caspase-3 after binding to the tetrameric β-galactosidase protein. We now demonstrate that co-expressing an anti-RAS heavy chain single VH domain, that binds to mutant RAS several thousand times more strongly than to wild type RAS, with a complementary light chain VL domain, caused programmed cell death (PCD) in mutant RAS expressing cells when each variable region is fused to procaspase-3. The effect requires binding of both anti-RAS variable region fragments and is RAS-specific, producing a tri-molecular complex that auto-activates the caspase pathway leading to cell death. AIDA can be generally applicable for any target protein inside cells by involving appropriate pairs of antigen-specific intracellular antibodies.en_US
dc.formatElectronicen_US
dc.format.extent8553 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleCancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-05-27en_US
rioxxterms.versionofrecord10.1038/s41598-019-44908-7en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2019-06-12en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfScientific reportsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Chromosomal Translocations and Intracellular Antibody Therapeutics
pubs.publication-statusPublisheden_US
pubs.volume9en_US
pubs.embargo.termsNot knownen_US
icr.researchteamChromosomal Translocations and Intracellular Antibody Therapeuticsen_US
dc.contributor.icrauthorRabbitts, Terenceen_US


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