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Related Experiment Videos

Targeting CD157 in AML using a novel, Fc-engineered antibody construct.

Christina Krupka1,2,3, Felix S Lichtenegger1,2,3, Thomas Köhnke1,2,3

  • 1Department of Internal Medicine III, Klinikum of The LMU Munich, Munich, Germany.

Oncotarget
|April 19, 2017
PubMed
Summary

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A novel antibody targeting CD157, MEN1112, shows promise for treating acute myeloid leukemia (AML). This engineered antibody effectively triggers natural killer cells to kill AML cells, including leukemia-initiating cells.

Area of Science:

  • Immunology
  • Hematology
  • Oncology

Background:

  • Antibody-based immunotherapy is a key strategy for treating acute myeloid leukemia (AML).
  • Chemorefractory leukemic cells pose a significant challenge in AML treatment.
  • CD157 is a potential target for novel immunotherapies.

Purpose of the Study:

  • To evaluate the efficacy of a novel Fc-engineered antibody, MEN1112, targeting CD157 for AML immunotherapy.
  • To assess CD157 expression levels in AML patient samples and leukemia-initiating cells.
  • To investigate the mechanism of action of MEN1112, including natural killer (NK) cell-mediated cytotoxicity.

Main Methods:

  • Expression analysis of CD157 in primary AML samples and healthy bone marrow.
  • Ex vivo assessment of MEN1112-induced cytotoxicity against AML cell lines and primary cells using NK cells.
Keywords:
AMLAntibodyCD157Fc-engineeringImmunotherapy

Related Experiment Videos

  • Comparison of Fc-engineered MEN1112 with its parental analogue.
  • Main Results:

    • CD157 is highly expressed in 97% of primary AML samples and on leukemia-initiating cells.
    • MEN1112 demonstrated significant NK cell-mediated cytotoxicity against AML cells.
    • Fc-engineering enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to the parental antibody.
    • Cytotoxicity varied among AML patients due to intrinsic NK cell defects.

    Conclusions:

    • CD157 is a relevant target for AML immunotherapy.
    • MEN1112 is a promising therapeutic candidate for AML, warranting further clinical investigation.
    • Patient-specific NK cell function and potential combinatorial strategies may influence treatment outcomes.