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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
Summary
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.
- 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.