Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins

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Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins. / Schieferdecker, Aneta; Shoshani, Ofer; Westner, Benedikt; Zipori, Dov; Fehse, Boris; Kröger, Nicolaus; Ayuketang, Francis Ayuk.

In: ONCOTARGET, Vol. 7, No. 41, 11.10.2016, p. 67061-67070.

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@article{274951a2b1e04451910d9e060190be62,
title = "Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins",
abstract = "INTRODUCTION: Multiple myeloma is still incurable in most cases. Polyclonal anti T lymphocyte globulins (ATG) have been reported to kill human myeloma cells in vitro and in mouse models.METHODS: Anti-human-myeloma globulins (AMG) were produced by immunizing rabbits with human myeloma cell lines RPMI-8226 (AMG-8226) or KMS-12-BM (AMG-12-BM). Cytotoxicity of the polyclonal antibodies was analyzed in vitro and in a xenograft NOD-SCID mouse model.RESULTS: Both AMG had stronger cytotoxicity against myeloma cells compared to ATG. In primary T cells, AMG-8226 showed greater complement-dependent cytotoxicity (CDC) than ATG, whereas complement-independent cytotoxicity did not differ. Effects on non-hematopoietic cell lines were also similar. Competitive blocking assays revealed fourfold more antibodies against CD38 in AMG-8226 compared to ATG. Low concentrations of AMG-8226 and ATG increased ADCC. At higher concentrations, ATG inhibited ADCC more potently than AMG-8226. Combinations of ATG and AMG-8226 with melphalan or bortezomib showed additive to synergistic cytotoxicity on myeloma cells. The cytotoxic effects of AMG and ATG were confirmed in the xenograft NOD-SCID mouse model.CONCLUSION: Our data show more potent antimyeloma effects of AMG compared to ATG. These results lay the ground for the development of polyclonal antibodies for the treatment of multiple myeloma.",
author = "Aneta Schieferdecker and Ofer Shoshani and Benedikt Westner and Dov Zipori and Boris Fehse and Nicolaus Kr{\"o}ger and Ayuketang, {Francis Ayuk}",
year = "2016",
month = oct,
day = "11",
doi = "10.18632/oncotarget.11489",
language = "English",
volume = "7",
pages = "67061--67070",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "41",

}

RIS

TY - JOUR

T1 - Potent in vitro and in vivo effects of polyclonal anti-human-myeloma globulins

AU - Schieferdecker, Aneta

AU - Shoshani, Ofer

AU - Westner, Benedikt

AU - Zipori, Dov

AU - Fehse, Boris

AU - Kröger, Nicolaus

AU - Ayuketang, Francis Ayuk

PY - 2016/10/11

Y1 - 2016/10/11

N2 - INTRODUCTION: Multiple myeloma is still incurable in most cases. Polyclonal anti T lymphocyte globulins (ATG) have been reported to kill human myeloma cells in vitro and in mouse models.METHODS: Anti-human-myeloma globulins (AMG) were produced by immunizing rabbits with human myeloma cell lines RPMI-8226 (AMG-8226) or KMS-12-BM (AMG-12-BM). Cytotoxicity of the polyclonal antibodies was analyzed in vitro and in a xenograft NOD-SCID mouse model.RESULTS: Both AMG had stronger cytotoxicity against myeloma cells compared to ATG. In primary T cells, AMG-8226 showed greater complement-dependent cytotoxicity (CDC) than ATG, whereas complement-independent cytotoxicity did not differ. Effects on non-hematopoietic cell lines were also similar. Competitive blocking assays revealed fourfold more antibodies against CD38 in AMG-8226 compared to ATG. Low concentrations of AMG-8226 and ATG increased ADCC. At higher concentrations, ATG inhibited ADCC more potently than AMG-8226. Combinations of ATG and AMG-8226 with melphalan or bortezomib showed additive to synergistic cytotoxicity on myeloma cells. The cytotoxic effects of AMG and ATG were confirmed in the xenograft NOD-SCID mouse model.CONCLUSION: Our data show more potent antimyeloma effects of AMG compared to ATG. These results lay the ground for the development of polyclonal antibodies for the treatment of multiple myeloma.

AB - INTRODUCTION: Multiple myeloma is still incurable in most cases. Polyclonal anti T lymphocyte globulins (ATG) have been reported to kill human myeloma cells in vitro and in mouse models.METHODS: Anti-human-myeloma globulins (AMG) were produced by immunizing rabbits with human myeloma cell lines RPMI-8226 (AMG-8226) or KMS-12-BM (AMG-12-BM). Cytotoxicity of the polyclonal antibodies was analyzed in vitro and in a xenograft NOD-SCID mouse model.RESULTS: Both AMG had stronger cytotoxicity against myeloma cells compared to ATG. In primary T cells, AMG-8226 showed greater complement-dependent cytotoxicity (CDC) than ATG, whereas complement-independent cytotoxicity did not differ. Effects on non-hematopoietic cell lines were also similar. Competitive blocking assays revealed fourfold more antibodies against CD38 in AMG-8226 compared to ATG. Low concentrations of AMG-8226 and ATG increased ADCC. At higher concentrations, ATG inhibited ADCC more potently than AMG-8226. Combinations of ATG and AMG-8226 with melphalan or bortezomib showed additive to synergistic cytotoxicity on myeloma cells. The cytotoxic effects of AMG and ATG were confirmed in the xenograft NOD-SCID mouse model.CONCLUSION: Our data show more potent antimyeloma effects of AMG compared to ATG. These results lay the ground for the development of polyclonal antibodies for the treatment of multiple myeloma.

U2 - 10.18632/oncotarget.11489

DO - 10.18632/oncotarget.11489

M3 - SCORING: Journal article

C2 - 27563813

VL - 7

SP - 67061

EP - 67070

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 41

ER -