dc.contributor.author | Zhang, J | |
dc.contributor.author | Jain, A | |
dc.contributor.author | Milhas, S | |
dc.contributor.author | Williamson, DJ | |
dc.contributor.author | Mysliwy, J | |
dc.contributor.author | Lodge, A | |
dc.contributor.author | Thirlway, J | |
dc.contributor.author | Al Nakeeb, M | |
dc.contributor.author | Miller, A | |
dc.contributor.author | Rabbitts, TH | |
dc.date.accessioned | 2021-08-04T09:43:34Z | |
dc.date.available | 2021-08-04T09:43:34Z | |
dc.date.issued | 2021-09-01 | |
dc.identifier.citation | Leukemia research, 2021, 108 pp. 106626 - ? | |
dc.identifier.issn | 0145-2126 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4720 | |
dc.identifier.eissn | 1873-5835 | |
dc.identifier.doi | 10.1016/j.leukres.2021.106626 | |
dc.description.abstract | 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 therapy targets to reduce tumour burden but also target the leukaemia-initiating cells from which tumours recur. Recent studies of the T cell leukaemia surfaceome confirmed that CD7 is highly expressed in overt disease. We have used an anti-CD7 antibody drug conjugate (ADC) to show that the binding of antibody to surface CD7 protein results in rapid internalization of the antigen together with the ADC. As a consequence, cell killing was observed via induction of apoptosis and was dependent on cell surface CD7. The in vitro cytotoxic activity (EC50) of the anti-CD7 ADC on T cell acute leukaemia (T-ALL) cells Jurkat and KOPT-K1 was found to be in the range of 5-8 ng/mL. In a pre-clinical xenograft model of human tumour growth expressing CD7 antigen, growth was curtailed by a single dose of ADC. The data indicate that CD7 targeting ADCs may be developed into an important second stage therapy for T cell acute leukaemia, for refractory CD7-positive leukaemias and for subsets of acute myeloid leukaemia (AML) expressing CD7. | |
dc.format | Print-Electronic | |
dc.format.extent | 106626 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | An antibody-drug conjugate with intracellular drug release properties showing specific cytotoxicity against CD7-positive cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-05-14 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.leukres.2021.106626 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-05-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Leukemia research | |
pubs.notes | Not known | |
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.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-status | Published | |
pubs.volume | 108 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Chromosomal Translocations and Intracellular Antibody Therapeutics | |
icr.researchteam | Chromosomal Translocations and Intracellular Antibody Therapeutics | |
dc.contributor.icrauthor | Rabbitts, Terence | |