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An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia

Standard

An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia. / Koerner, S P; André, M C; Leibold, J S; Kousis, P C; Kübler, A; Pal, M; Haen, S P; Bühring, H-J; Grosse-Hovest, L; Jung, G; Salih, H R.

in: LEUKEMIA, Jahrgang 31, Nr. 2, 02.2017, S. 459-469.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Koerner, SP, André, MC, Leibold, JS, Kousis, PC, Kübler, A, Pal, M, Haen, SP, Bühring, H-J, Grosse-Hovest, L, Jung, G & Salih, HR 2017, 'An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia', LEUKEMIA, Jg. 31, Nr. 2, S. 459-469. https://doi.org/10.1038/leu.2016.194

APA

Koerner, S. P., André, M. C., Leibold, J. S., Kousis, P. C., Kübler, A., Pal, M., Haen, S. P., Bühring, H-J., Grosse-Hovest, L., Jung, G., & Salih, H. R. (2017). An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia. LEUKEMIA, 31(2), 459-469. https://doi.org/10.1038/leu.2016.194

Vancouver

Koerner SP, André MC, Leibold JS, Kousis PC, Kübler A, Pal M et al. An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia. LEUKEMIA. 2017 Feb;31(2):459-469. https://doi.org/10.1038/leu.2016.194

Bibtex

@article{59c0a379caa847cfb1c72fb608f045aa,
title = "An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia",
abstract = "Antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells largely contributes to the success of monoclonal antibody (mAb) treatment in cancer. As no antibodies are clinically available for immunotherapy of myeloid leukemias (MLs), we aimed to develop an Fc-optimized CD133 mAb for induction of NK ADCC against MLs. When comparing different available CD133 mAbs, no difference was observed with regard to binding to primary chronic myeloid leukemia cells. However, clone 293C3 recognized acute myeloid leukemia (AML) cells in a substantially higher percentage of patient cases and was thus chosen to generate chimeric mAbs with either wild-type Fc part (293C3-WT) or a variant containing amino-acid exchanges (S239D/I332E) to enhance affinity to CD16 on NK cells (293C3-SDIE). In vitro, treatment with 293C3-SDIE significantly enhanced activation, degranulation and lysis of primary CD133-positive AML cells by allogeneic and autologous NK cells as compared with its wild-type counterpart. In line with the observed lower expression levels of CD133 on healthy cells compared with malignant hematopoietic cells, 293C3-SDIE caused no relevant toxicity towards committed hematopoietic progenitor cells. In a NOD.Cg-PrkdcscidIL2rgtmWjl/Sz xenotransplantation model, 293C3-SDIE facilitated elimination of patient AML cells by human NK cells. Thus, 293C3-SDIE constitutes an attractive immunotherapeutic compound, in particular for elimination of minimal residual disease in the context of allogeneic stem cell transplantation in AML.",
keywords = "AC133 Antigen/immunology, Animals, Antibodies, Monoclonal/immunology, Antibody-Dependent Cell Cytotoxicity, Cell Degranulation/immunology, Cytokines/metabolism, Cytotoxicity, Immunologic/immunology, Epitopes/immunology, Heterografts, Humans, Immunoglobulin Fc Fragments/immunology, Killer Cells, Natural/immunology, Leukemia, Myeloid, Acute/immunology, Lymphocyte Activation/immunology, Mice",
author = "Koerner, {S P} and Andr{\'e}, {M C} and Leibold, {J S} and Kousis, {P C} and A K{\"u}bler and M Pal and Haen, {S P} and H-J B{\"u}hring and L Grosse-Hovest and G Jung and Salih, {H R}",
year = "2017",
month = feb,
doi = "10.1038/leu.2016.194",
language = "English",
volume = "31",
pages = "459--469",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - An Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia

AU - Koerner, S P

AU - André, M C

AU - Leibold, J S

AU - Kousis, P C

AU - Kübler, A

AU - Pal, M

AU - Haen, S P

AU - Bühring, H-J

AU - Grosse-Hovest, L

AU - Jung, G

AU - Salih, H R

PY - 2017/2

Y1 - 2017/2

N2 - Antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells largely contributes to the success of monoclonal antibody (mAb) treatment in cancer. As no antibodies are clinically available for immunotherapy of myeloid leukemias (MLs), we aimed to develop an Fc-optimized CD133 mAb for induction of NK ADCC against MLs. When comparing different available CD133 mAbs, no difference was observed with regard to binding to primary chronic myeloid leukemia cells. However, clone 293C3 recognized acute myeloid leukemia (AML) cells in a substantially higher percentage of patient cases and was thus chosen to generate chimeric mAbs with either wild-type Fc part (293C3-WT) or a variant containing amino-acid exchanges (S239D/I332E) to enhance affinity to CD16 on NK cells (293C3-SDIE). In vitro, treatment with 293C3-SDIE significantly enhanced activation, degranulation and lysis of primary CD133-positive AML cells by allogeneic and autologous NK cells as compared with its wild-type counterpart. In line with the observed lower expression levels of CD133 on healthy cells compared with malignant hematopoietic cells, 293C3-SDIE caused no relevant toxicity towards committed hematopoietic progenitor cells. In a NOD.Cg-PrkdcscidIL2rgtmWjl/Sz xenotransplantation model, 293C3-SDIE facilitated elimination of patient AML cells by human NK cells. Thus, 293C3-SDIE constitutes an attractive immunotherapeutic compound, in particular for elimination of minimal residual disease in the context of allogeneic stem cell transplantation in AML.

AB - Antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells largely contributes to the success of monoclonal antibody (mAb) treatment in cancer. As no antibodies are clinically available for immunotherapy of myeloid leukemias (MLs), we aimed to develop an Fc-optimized CD133 mAb for induction of NK ADCC against MLs. When comparing different available CD133 mAbs, no difference was observed with regard to binding to primary chronic myeloid leukemia cells. However, clone 293C3 recognized acute myeloid leukemia (AML) cells in a substantially higher percentage of patient cases and was thus chosen to generate chimeric mAbs with either wild-type Fc part (293C3-WT) or a variant containing amino-acid exchanges (S239D/I332E) to enhance affinity to CD16 on NK cells (293C3-SDIE). In vitro, treatment with 293C3-SDIE significantly enhanced activation, degranulation and lysis of primary CD133-positive AML cells by allogeneic and autologous NK cells as compared with its wild-type counterpart. In line with the observed lower expression levels of CD133 on healthy cells compared with malignant hematopoietic cells, 293C3-SDIE caused no relevant toxicity towards committed hematopoietic progenitor cells. In a NOD.Cg-PrkdcscidIL2rgtmWjl/Sz xenotransplantation model, 293C3-SDIE facilitated elimination of patient AML cells by human NK cells. Thus, 293C3-SDIE constitutes an attractive immunotherapeutic compound, in particular for elimination of minimal residual disease in the context of allogeneic stem cell transplantation in AML.

KW - AC133 Antigen/immunology

KW - Animals

KW - Antibodies, Monoclonal/immunology

KW - Antibody-Dependent Cell Cytotoxicity

KW - Cell Degranulation/immunology

KW - Cytokines/metabolism

KW - Cytotoxicity, Immunologic/immunology

KW - Epitopes/immunology

KW - Heterografts

KW - Humans

KW - Immunoglobulin Fc Fragments/immunology

KW - Killer Cells, Natural/immunology

KW - Leukemia, Myeloid, Acute/immunology

KW - Lymphocyte Activation/immunology

KW - Mice

U2 - 10.1038/leu.2016.194

DO - 10.1038/leu.2016.194

M3 - SCORING: Journal article

C2 - 27435001

VL - 31

SP - 459

EP - 469

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 2

ER -