TY - JOUR
T1 - In vivo assay of human NK-dependent ADCC using NOD/SCID/γcnull (NOG) mice
AU - Shiokawa, Miho
AU - Takahashi, Takeshi
AU - Murakami, Akihiro
AU - Kita, Shoichi
AU - Ito, Mamoru
AU - Sugamura, Kazuo
AU - Ishii, Naoto
N1 - Funding Information:
We thank Dr. I. Yahara for discussion and also thank to M. Ito and K. Kudomi for the technical assistance. This work was supported in part by a grant-in-aid for scientific research on priority areas , and a grant-in-aid for scientific research (S) from the Japan Society for the Promotion of Science to K.S. and M.I.
PY - 2010/9
Y1 - 2010/9
N2 - Monoclonal antibodies are essential to the success of molecularly targeted therapies. Recently, numerous therapeutic antibodies have been developed for various diseases, including cancer and autoimmune diseases. Experimental systems to effectively evaluate these candidate antibodies are urgently needed. One of the mechanisms used by antibodies to kill tumor cells is antibody-dependent cellular cytotoxicity (ADCC), in which natural killer cells (NK) are the main mediator. The capacity to induce ADCC has conventionally been assessed in the human-mouse xeno-graft model, in which human peripheral blood mononuclear cells (PBMC), containing NK cells along with antibodies, are administered to tumor-bearing immunodeficient mice. However, contamination from other cellular populations often affects tumor growth, making it difficult to evaluate the antibody's effect. In this study, we established a new NK-dependent ADCC assay model using a supra-immunodeficient strain of mice, NOD/SCID/γcnull (NOG). Our model system simply consisted of three elements: isolated human NK cells, a Burkitt's lymphoma cell line (Daudi), and an anti-CD20 antibody (Rituximab). In this experimental setting, human NK cells from healthy donors retained their killing activity and suppressed the growth of Daudi cells in NOG mice when they were administered along with Rituximab. This system, therefore, is useful for evaluating the in vivo function of human NK cells.
AB - Monoclonal antibodies are essential to the success of molecularly targeted therapies. Recently, numerous therapeutic antibodies have been developed for various diseases, including cancer and autoimmune diseases. Experimental systems to effectively evaluate these candidate antibodies are urgently needed. One of the mechanisms used by antibodies to kill tumor cells is antibody-dependent cellular cytotoxicity (ADCC), in which natural killer cells (NK) are the main mediator. The capacity to induce ADCC has conventionally been assessed in the human-mouse xeno-graft model, in which human peripheral blood mononuclear cells (PBMC), containing NK cells along with antibodies, are administered to tumor-bearing immunodeficient mice. However, contamination from other cellular populations often affects tumor growth, making it difficult to evaluate the antibody's effect. In this study, we established a new NK-dependent ADCC assay model using a supra-immunodeficient strain of mice, NOD/SCID/γcnull (NOG). Our model system simply consisted of three elements: isolated human NK cells, a Burkitt's lymphoma cell line (Daudi), and an anti-CD20 antibody (Rituximab). In this experimental setting, human NK cells from healthy donors retained their killing activity and suppressed the growth of Daudi cells in NOG mice when they were administered along with Rituximab. This system, therefore, is useful for evaluating the in vivo function of human NK cells.
KW - Antibody
KW - Antibody-dependent cellular cytotoxicity (ADCC)
KW - NK cell
KW - NOG mice
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U2 - 10.1016/j.bbrc.2010.07.145
DO - 10.1016/j.bbrc.2010.07.145
M3 - Article
C2 - 20696130
AN - SCOPUS:77956261949
VL - 399
SP - 733
EP - 737
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -