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

Marijn A. Gillissen; Greta de Jong; Martijn Kedde; Etsuko Yasuda; Sophie E. Levie; Gemma Moiset; Paul J. Hensbergen; Arjen Q. Bakker; Koen Wagner; Jullien Villaudy; Pauline M. van Helden; Hergen Spits; Mette D. Hazenberg

doi:https://doi.org/10.1182/bloodadvances.2017008342

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

Marijn A. Gillissen, Greta de Jong, Martijn Kedde, Etsuko Yasuda, Sophie E. Levie, Gemma Moiset, Paul J. Hensbergen, Arjen Q. Bakker, Koen Wagner, Jullien Villaudy, Pauline M. van Helden, Hergen Spits, Mette D. Hazenberg

Research output: Contribution to journal › Article › Academic › peer-review

19 Citations (Scopus)

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

Original language	English
Pages (from-to)	1551-1564
Journal	Blood advances
Volume	1
Issue number	19
DOIs	https://doi.org/10.1182/bloodadvances.2017008342
Publication status	Published - 2017

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https://doi.org/10.1182/bloodadvances.2017008342

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Gillissen, M. A., de Jong, G., Kedde, M., Yasuda, E., Levie, S. E., Moiset, G., Hensbergen, P. J., Bakker, A. Q., Wagner, K., Villaudy, J., van Helden, P. M., Spits, H., & Hazenberg, M. D. (2017). Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice. Blood advances, 1(19), 1551-1564. https://doi.org/10.1182/bloodadvances.2017008342

@article{957fed7903b644dba89f92d5b0a09e0f,

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

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",

author = "Gillissen, {Marijn A.} and {de Jong}, Greta and Martijn Kedde and Etsuko Yasuda and Levie, {Sophie E.} and Gemma Moiset and Hensbergen, {Paul J.} and Bakker, {Arjen Q.} and Koen Wagner and Jullien Villaudy and {van Helden}, {Pauline M.} and Hergen Spits and Hazenberg, {Mette D.}",

year = "2017",

doi = "https://doi.org/10.1182/bloodadvances.2017008342",

language = "English",

volume = "1",

pages = "1551--1564",

journal = "Blood advances",

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publisher = "American Society of Hematology",

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Gillissen, MA, de Jong, G, Kedde, M, Yasuda, E, Levie, SE, Moiset, G, Hensbergen, PJ, Bakker, AQ, Wagner, K, Villaudy, J, van Helden, PM, Spits, H & Hazenberg, MD 2017, 'Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice', Blood advances, vol. 1, no. 19, pp. 1551-1564. https://doi.org/10.1182/bloodadvances.2017008342

TY - JOUR

T1 - Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice

AU - Gillissen, Marijn A.

AU - de Jong, Greta

AU - Kedde, Martijn

AU - Yasuda, Etsuko

AU - Levie, Sophie E.

AU - Moiset, Gemma

AU - Hensbergen, Paul J.

AU - Bakker, Arjen Q.

AU - Wagner, Koen

AU - Villaudy, Jullien

AU - van Helden, Pauline M.

AU - Spits, Hergen

AU - Hazenberg, Mette D.

PY - 2017

Y1 - 2017

N2 - 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

AB - 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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DO - https://doi.org/10.1182/bloodadvances.2017008342

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SN - 2473-9529

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SP - 1551

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JO - Blood advances

JF - Blood advances

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