TY - JOUR
T1 - Harnessing the innate immune system to treat cancer
T2 - Enhancement of antibody-dependent cellular cytotoxicity with anti-CD137 Ab
AU - Yonezawa, Atsushi
AU - Chester, Cariad
AU - Rajasekaran, Narendiran
AU - Kohrt, Holbrook E.
N1 - Publisher Copyright:
© Chinese Clinical Oncology. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Background: Monoclonal antibodies are an invaluable therapeutic class when it comes to cancer therapy. One of the primary mechanisms of anti-tumor activity of monoclonal antibodies is antibody dependent cell-mediated cytotoxicity (ADCC) mediated by natural killer (NK) cells. Innate immune effector cells play important roles in generating and maintaining antitumor immunity to enhance ADCC. Methods: Efficacy of anti-CD137 mAb was examined by in vitro and in vivo experiments. Clinical trials of anti-CD137 mAb are also on-going. Results: CD137 is a costimulatory receptor that belongs to the tumor necrosis factor receptor (TNFR) superfamily. CD137 is expressed on T cell, activated NK cells and other immune cells. We recently showed that an agonistic anti-CD137 mAb activates NK cells, resulting in increased ADCC against cancer cells. Anti-CD137 agonistic mAb therapy may both increase ADCC due to mAb-activated NK cells and promote the proliferation and cytotoxicity of antigen-specific T cells induced by mAb treatment. Conclusions: We discuss some of the promising strategies that could potentially enhance ADCC with anti-CD137 mAbs.
AB - Background: Monoclonal antibodies are an invaluable therapeutic class when it comes to cancer therapy. One of the primary mechanisms of anti-tumor activity of monoclonal antibodies is antibody dependent cell-mediated cytotoxicity (ADCC) mediated by natural killer (NK) cells. Innate immune effector cells play important roles in generating and maintaining antitumor immunity to enhance ADCC. Methods: Efficacy of anti-CD137 mAb was examined by in vitro and in vivo experiments. Clinical trials of anti-CD137 mAb are also on-going. Results: CD137 is a costimulatory receptor that belongs to the tumor necrosis factor receptor (TNFR) superfamily. CD137 is expressed on T cell, activated NK cells and other immune cells. We recently showed that an agonistic anti-CD137 mAb activates NK cells, resulting in increased ADCC against cancer cells. Anti-CD137 agonistic mAb therapy may both increase ADCC due to mAb-activated NK cells and promote the proliferation and cytotoxicity of antigen-specific T cells induced by mAb treatment. Conclusions: We discuss some of the promising strategies that could potentially enhance ADCC with anti-CD137 mAbs.
KW - Antibody dependent cell-mediated cytotoxicity (ADCC)
KW - CD137
KW - Cancer immunotherapy
KW - Natural killer cells (NK cells)
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U2 - 10.3978/j.issn.2304-3865.2016.02.05
DO - 10.3978/j.issn.2304-3865.2016.02.05
M3 - Article
C2 - 26932429
AN - SCOPUS:84966429497
SN - 2304-3865
VL - 5
JO - Chinese Clinical Oncology
JF - Chinese Clinical Oncology
IS - 1
M1 - 5
ER -