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, Jahrgang 7, Nr. 41, 11.10.2016, S. 67061-67070.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -