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Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice. / Gillissen, Marijn A.; de Jong, Greta; Kedde, Martijn et al.

In: Blood advances, Vol. 1, No. 19, 2017, p. 1551-1564.

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@article{7ed7de99ec9b4ddc9d27c3b114717d21,
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 = "10.1182/bloodadvances.2017008342",
language = "English",
volume = "1",
pages = "1551--1564",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "19",

}

RIS

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

U2 - 10.1182/bloodadvances.2017008342

DO - 10.1182/bloodadvances.2017008342

M3 - Article

C2 - 29296797

VL - 1

SP - 1551

EP - 1564

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 19

ER -

ID: 4102248