Open AccessAntibody‐dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant natural killer T cells
Author(s) -
Mise Naoko,
Takami Mariko,
Suzuki Akane,
Kamata Toshiko,
Harada Kazuaki,
Hishiki Tomoro,
Saito Takeshi,
Terui Keita,
Mitsunaga Tetsuya,
Nakata Mitsuyuki,
Ikeuchi Takayuki,
Nakayama Toshinori,
Yoshida Hideo,
Motohashi Shinichiro
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12882
Subject(s) - antibody dependent cell mediated cytotoxicity , granzyme , natural killer t cell , granzyme b , lymphokine activated killer cell , cytotoxic t cell , immunology , cytotoxicity , antibody , nk 92 , immunotherapy , biology , natural killer cell , cancer research , interleukin 21 , perforin , immune system , t cell , cd8 , monoclonal antibody , in vitro , biochemistry
Anti‐ganglioside GD2 antibodies mainly work through antibody‐dependent cellular cytotoxicity (ADCC) and have demonstrated clinical benefit for children with neuroblastoma. However, high‐risk neuroblastoma still has a high recurrence rate. For further improvement in patient outcomes, ways to maximize the cytotoxic effects of anti‐GD2 therapies with minimal toxicity are required. Activated invariant natural killer T (iNKT) cells enhance both innate and type I acquired anti‐tumor immunity by producing several kinds of cytokines. In this report, we investigated the feasibility of combination therapy using iNKT cells and an anti‐GD2 antibody. Although some of the expanded iNKT cells expressed natural killer (NK) cell markers, including FcγR, iNKT cells were not directly associated with ADCC. When co‐cultured with activated iNKT cells, granzyme A, granzyme B and interferon gamma (IFNγ) production from NK cells were upregulated, and the cytotoxicity of NK cells treated with anti‐GD2 antibodies was increased. Not only cytokines produced by activated iNKT cells, but also NK‐NKT cell contact or NK cell‐dendritic cell contact contributed to the increase in NK cell cytotoxicity and further IFNγ production by iNKT cells and NK cells. In conclusion, iNKT cell‐based immunotherapy could be an appropriate candidate for anti‐GD2 antibody therapy for neuroblastoma.