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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 ...

  • 2022-02-10
  • Ferrata Storti Foundation (Haematologica),2022
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-317010
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-317010URI
  • https://doi.org/10.3324/haematol.2021.279486DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150533442URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20220906
  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Stikvoort, ArwenKarolinska Institutet (author)
  • Lambert, MelanieKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden. (author)
  • Jin, LiqingUniv Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. (author)
  • Sanchez-Rivera, LauraKTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u13bwsp9 (author)
  • Alves, Renato M. P.KTH,Tillämpad fysik,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1bengi4 (author)
  • de Moura, Tales RochaKTH,Medicinteknik och hälsosystem(Swepub:kth)u1vpkwih (author)
  • Mim, CarstenKTH,Strukturell bioteknik(Swepub:kth)u1ce0qjf (author)
  • Lehmann, SorenKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden. (author)
  • Axelsson-Robertson, RebeccaKarolinska Institutet (author)
  • Dick, John E.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.;Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. (author)
  • Mattsson, JonasKarolinska Institutet (author)
  • 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)
  • Carlsten, MattiasKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Cell Therapy & Allogene Stem Cell Transplanta, Stockholm, Sweden. (author)
  • 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)
  • Karolinska InstitutetKarolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden. (creator_code:org_t)

Related titles

  • In:Haematologica: Ferrata Storti Foundation (Haematologica)107:8, s. 1786-17950390-60781592-8721

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