Search: id:"swepub:oai:DiVA.org:kth-317010" >
A novel CD34-specif...
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Arruda, Lucas C. M.Karolinska Institutet
(author)
A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells in vitro and in vivo
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-02-10
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Ferrata Storti Foundation (Haematologica),2022
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:kth-317010
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-317010URI
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https://doi.org/10.3324/haematol.2021.279486DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:150533442URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20220906
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Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34(+) blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34(+)CD38(-) phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo. Our results show that this CD34-specific BTE induces CD34-dependent T-cell activation and subsequent leukemia cell killing in a dose-dependent manner, further corroborated by enhanced T-cell-mediated killing at the singlecell level. Additionally, the BTE triggered efficient T-cell-mediated depletion of CD34(+) hematopoietic stem cells from peripheral blood stem cell grafts and CD34(+) blasts from AML patients. Using a humanized AML xenograft model, we confirmed that the CD34-specific BTE had in vivo efficacy by depleting CD34(+) blasts and leukemic stem cells without side effects. Taken together, these data demonstrate that the CD34-specific BTE has robust antitumor effects, supporting development of a novel treatment modality with the aim of improving outcomes of patients with AML and myelodysplastic syndromes.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Stikvoort, ArwenKarolinska Institutet
(author)
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Lambert, MelanieKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden.
(author)
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Jin, LiqingUniv Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
(author)
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Sanchez-Rivera, LauraKTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u13bwsp9
(author)
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Alves, Renato M. P.KTH,Tillämpad fysik,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1bengi4
(author)
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de Moura, Tales RochaKTH,Medicinteknik och hälsosystem(Swepub:kth)u1vpkwih
(author)
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Mim, CarstenKTH,Strukturell bioteknik(Swepub:kth)u1ce0qjf
(author)
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Lehmann, SorenKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden.
(author)
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Axelsson-Robertson, RebeccaKarolinska Institutet
(author)
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Dick, John E.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.;Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
(author)
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Mattsson, JonasKarolinska Institutet
(author)
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Önfelt, BjörnKTH,Tillämpad fysik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Sci Life Lab, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.(Swepub:kth)u1tquq43
(author)
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Carlsten, MattiasKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Cell Therapy & Allogene Stem Cell Transplanta, Stockholm, Sweden.
(author)
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Uhlin, MichaelKarolinska Institutet,KTH,Biofysik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.; Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden.(Swepub:kth)u1ira0gr
(author)
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Karolinska InstitutetKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden.
(creator_code:org_t)
Related titles
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In:Haematologica: Ferrata Storti Foundation (Haematologica)107:8, s. 1786-17950390-60781592-8721
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- By the author/editor
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Arruda, Lucas C. ...
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Stikvoort, Arwen
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Lambert, Melanie
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Jin, Liqing
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Sanchez-Rivera, ...
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Alves, Renato M. ...
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de Moura, Tales ...
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Mim, Carsten
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Lehmann, Soren
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Axelsson-Roberts ...
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Dick, John E.
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Mattsson, Jonas
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Önfelt, Björn
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Carlsten, Mattia ...
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Uhlin, Michael
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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MEDICAL AND HEAL ...
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and Respiratory Medi ...
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MEDICAL AND HEAL ...
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and Cancer and Oncol ...
- Articles in the publication
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Haematologica
- By the university
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Royal Institute of Technology
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Karolinska Institutet