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New anti-IL-7Ra monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models

  1. Author:
    Hixon,Julie
    Andrews,Caroline
    Kashi, Lila
    Kohnhorst, Casey L
    Senkevitch, Emilee
    Czarra,Kelli
    Barata, Joao T [ORCID]
    Li,Wenqing
    Schneider,Joel
    Walsh,Scott
    Durum,Scott

  2. Author Address

    Cytokines and Immunity Section, Cancer and Inflammation Program (CIP), National Cancer Institute (NCI), National Institutes of Health (NIH), Frederick, MD, USA., Comparative Biomedical Scientist Training Program, NIH, Bethesda, MD, USA., Michigan State University, East Lansing, MI, USA., Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA., Cancer Biology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal., Chemical Biology Laboratory, NCI, NIH, Frederick, MD, USA., Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA. walshst@nih.gov., Chemical Biology Laboratory, NCI, NIH, Frederick, MD, USA. walshst@nih.gov., Cytokines and Immunity Section, Cancer and Inflammation Program (CIP), National Cancer Institute (NCI), National Institutes of Health (NIH), Frederick, MD, USA. durums@mail.nih.gov.,
    1. Year: 2020
    2. Date: JAN
    3. Epub Date: 2019 08 22
  2. Journal: Leukemia
    1. 34
    2. 1
    3. Pages: 35-49
  4. Type of Article: Article
  5. ISSN: 0887-6924
  1. Abstract:

    Pediatric T cell acute lymphoblastic leukemia (T-ALL) cells frequently contain mutations in the interleukin-7 (IL-7) receptor pathway or respond to IL-7 itself. To target the IL-7 receptor on T-ALL cells, murine monoclonal antibodies (MAbs) were developed against the human IL-7Ra chain and chimerized with human IgG1 constant regions. Crystal structures demonstrate that the two MAbs bound different IL-7Ra epitopes. The MAbs mediated antibody-dependent cell-mediated cytotoxicity (ADCC) against patient-derived xenograft (PDX) T-ALL cells, which was improved by combining two MAbs. In vivo, the MAbs showed therapeutic efficacy via ADCC-dependent and independent mechanisms in minimal residual and established disease. PDX T-ALL cells that relapsed following a course of chemotherapy displayed elevated IL-7Ra, and MAb treatment is effective against relapsing disease, suggesting the use of anti-IL7Ra MAbs in relapsed T-ALL patients or patients that do not respond to chemotherapy.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41375-019-0531-8
  3. PMID: 31439943
  4. View record in Web of Science®
  5. WOS: 000523480000003
  6. PII : 10.1038/s41375-019-0531-8

Library Notes

  1. Fiscal Year: FY2018-2019
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