MDX-1097 induces antibody-dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

Parisa Asvadi, Andrew R Cuddihy, Rosanne Dunn, Vivien Jiang, Mae X Wong, Darren R Jones, Tiffany Tee Fern Khong, Andrew Spencer

Research output: Contribution to journalArticleResearchpeer-review

Abstract

MDX-1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane-associated free kappa light chain (?FLC). KMA was detected on kappa human multiple myeloma cell lines (?HMCLs), on plasma cells (PCs) from kappa multiple myeloma (?MM) patients and on ?PC dyscrasia tissue cryosections. In primary ?MM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX-1097 exhibited a higher affinity for KMA compared to ?FLC and the latter did not abrogate binding to KMA. MDX-1097-mediated antibody-dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX-1097-mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX-1097-mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX-1097. The ADCC-inducing capacity of MDX-1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX-1097 alone and in combination with lenalidomide.
Original languageEnglish
Pages (from-to)333 - 343
Number of pages11
JournalBritish Journal of Haematology
Volume169
Issue number3
DOIs
Publication statusPublished - 2015

Cite this

Asvadi, Parisa ; Cuddihy, Andrew R ; Dunn, Rosanne ; Jiang, Vivien ; Wong, Mae X ; Jones, Darren R ; Khong, Tiffany Tee Fern ; Spencer, Andrew. / MDX-1097 induces antibody-dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide. In: British Journal of Haematology. 2015 ; Vol. 169, No. 3. pp. 333 - 343.
@article{88c5c0dc571541eba481d43d7e7f72a9,
title = "MDX-1097 induces antibody-dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide",
abstract = "MDX-1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane-associated free kappa light chain (?FLC). KMA was detected on kappa human multiple myeloma cell lines (?HMCLs), on plasma cells (PCs) from kappa multiple myeloma (?MM) patients and on ?PC dyscrasia tissue cryosections. In primary ?MM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX-1097 exhibited a higher affinity for KMA compared to ?FLC and the latter did not abrogate binding to KMA. MDX-1097-mediated antibody-dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX-1097-mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX-1097-mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX-1097. The ADCC-inducing capacity of MDX-1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX-1097 alone and in combination with lenalidomide.",
author = "Parisa Asvadi and Cuddihy, {Andrew R} and Rosanne Dunn and Vivien Jiang and Wong, {Mae X} and Jones, {Darren R} and Khong, {Tiffany Tee Fern} and Andrew Spencer",
year = "2015",
doi = "10.1111/bjh.13298",
language = "English",
volume = "169",
pages = "333 -- 343",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons",
number = "3",

}

MDX-1097 induces antibody-dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide. / Asvadi, Parisa; Cuddihy, Andrew R; Dunn, Rosanne; Jiang, Vivien; Wong, Mae X; Jones, Darren R; Khong, Tiffany Tee Fern; Spencer, Andrew.

In: British Journal of Haematology, Vol. 169, No. 3, 2015, p. 333 - 343.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - MDX-1097 induces antibody-dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

AU - Asvadi, Parisa

AU - Cuddihy, Andrew R

AU - Dunn, Rosanne

AU - Jiang, Vivien

AU - Wong, Mae X

AU - Jones, Darren R

AU - Khong, Tiffany Tee Fern

AU - Spencer, Andrew

PY - 2015

Y1 - 2015

N2 - MDX-1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane-associated free kappa light chain (?FLC). KMA was detected on kappa human multiple myeloma cell lines (?HMCLs), on plasma cells (PCs) from kappa multiple myeloma (?MM) patients and on ?PC dyscrasia tissue cryosections. In primary ?MM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX-1097 exhibited a higher affinity for KMA compared to ?FLC and the latter did not abrogate binding to KMA. MDX-1097-mediated antibody-dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX-1097-mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX-1097-mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX-1097. The ADCC-inducing capacity of MDX-1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX-1097 alone and in combination with lenalidomide.

AB - MDX-1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane-associated free kappa light chain (?FLC). KMA was detected on kappa human multiple myeloma cell lines (?HMCLs), on plasma cells (PCs) from kappa multiple myeloma (?MM) patients and on ?PC dyscrasia tissue cryosections. In primary ?MM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX-1097 exhibited a higher affinity for KMA compared to ?FLC and the latter did not abrogate binding to KMA. MDX-1097-mediated antibody-dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX-1097-mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX-1097-mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX-1097. The ADCC-inducing capacity of MDX-1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX-1097 alone and in combination with lenalidomide.

UR - http://onlinelibrary.wiley.com/doi/10.1111/bjh.13298/epdf

U2 - 10.1111/bjh.13298

DO - 10.1111/bjh.13298

M3 - Article

VL - 169

SP - 333

EP - 343

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 3

ER -