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  • Ågerstam, HelenaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine (author)

Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia.

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2015-08-10
  • Proceedings of the National Academy of Sciences,2015
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:0c5154c0-8f8a-4061-9e5d-2f05e0072441
  • https://lup.lub.lu.se/record/7844248URI
  • https://doi.org/10.1073/pnas.1422749112DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Acute myeloid leukemia (AML) is associated with a poor survival rate, and there is an urgent need for novel and more efficient therapies, ideally targeting AML stem cells that are essential for maintaining the disease. The interleukin 1 receptor accessory protein (IL1RAP; IL1R3) is expressed on candidate leukemic stem cells in the majority of AML patients, but not on normal hematopoietic stem cells. We show here that monoclonal antibodies targeting IL1RAP have strong antileukemic effects in xenograft models of human AML. We demonstrate that effector-cell-mediated killing is essential for the observed therapeutic effects and that natural killer cells constitute a critical human effector cell type. Because IL-1 signaling is important for the growth of AML cells, we generated an IL1RAP-targeting antibody capable of blocking IL-1 signaling and show that this antibody suppresses the proliferation of primary human AML cells. Hence, IL1RAP can be efficiently targeted with an anti-IL1RAP antibody capable of both achieving antibody-dependent cellular cytotoxicity and blocking of IL-1 signaling as modes of action. Collectively, these results provide important evidence in support of IL1RAP as a target for antibody-based treatment of AML.

Subject headings and genre

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

  • Karlsson, ChristineLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)immu-cgl (author)
  • Hansen, NilsLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-nhn (author)
  • Sandén, CarlLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-cls (author)
  • Askmyr, MariaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-mj0 (author)
  • von Palffy, SofiaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-svf (author)
  • Högberg, CarlLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kard-clh (author)
  • Rissler, MarianneLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-mri (author)
  • Wunderlich, Mark (author)
  • Juliusson, GunnarLund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)stem-gju (author)
  • Richter, JohanLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-jri (author)
  • Sjöström, Kjell (author)
  • Bhatia, Ravi (author)
  • Mulloy, James C (author)
  • Järås, MarcusLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Målinriktade behandlingar för leukemi,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Targeted therapies in leukemia,Lund University Research Groups(Swepub:lu)molm-mn8 (author)
  • Fioretos, ThoasLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-tfi (author)
  • Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences112:34, s. 10786-107911091-64900027-8424

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