Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice

  • Blood Adv. 2017 Aug 18;1(19):1551-1564. doi: 10.1182/bloodadvances.2017008342.
Marijn A Gillissen  1  2 ,  Greta de Jong  1  2 ,  Martijn Kedde  1 ,  Etsuko Yasuda  1 ,  Sophie E Levie  1 ,  Gemma Moiset  1 ,  Paul J Hensbergen  3 ,  Arjen Q Bakker  1 ,  Koen Wagner  1 ,  Jullien Villaudy  1 ,  Pauline M van Helden  1 ,  Hergen Spits  1  4 ,  Mette D Hazenberg  2  4
Affiliations
  • 1. AIMM Therapeutics, Amsterdam, The Netherlands.
  • 2. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
  • 3. Center for Proteomics and Metabolomics, University Medical Center, Leiden, The Netherlands; and.
  • 4. Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
PMID: 29296797 DOI: 10.1182/bloodadvances.2017008342
Abstract

Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s). Strikingly, CD43s is expressed on all World Health Organization 2008 types of AML and MDS. AT1413 induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of AML cells in vitro. Of note, AT1413 was highly efficacious against AML cells in a humanized mouse model without affecting nonmalignant human myeloid cells, suggesting AT1413 has potential as a therapeutic antibody.

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