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In vivo antitumor function of tumor antigen‐specific CTLs generated in the presence of OX40 co‐stimulation in vitro
Author(s) -
Pham Minh Ngoc,
Murata Satoshi,
Kitamura Naomi,
Ueki Tomoyuki,
Kojima Masatsugu,
Miyake Toru,
Takebayashi Katsushi,
Kodama Hirokazu,
Mekata Eiji,
Tani Masaji
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31244
Subject(s) - cd8 , cytotoxic t cell , adoptive cell transfer , biology , immunotherapy , antigen , cancer research , monoclonal antibody , cancer immunotherapy , t cell , in vivo , in vitro , immunology , antibody , immune system , biochemistry , microbiology and biotechnology
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag‐specific effector CD8 + T‐cells, co‐cultured with a tumor‐specific peptide and a stimulatory anti‐OX40 antibody, before being used for ACT therapy in tumor‐bearing mouse recipients. Splenic T‐cells were obtained from wild‐type FVB/N mice that had been injected with a HER2/neu (neu)‐expressing tumor and a neu‐vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti‐OX40 monoclonal antibody, before CD8 + T cells were isolated for use in ACT therapy. The proliferative ability of OX40‐driven tumor Ag‐specific effector CD8 + T‐cells in vitro was less than that of non‐OX40‐driven tumor Ag‐specific effector CD8 + T‐cells, but they expressed significantly more early T‐cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl‐2, an anti‐apoptotic protein. These OX40‐driven tumor Ag‐specific effector CD8 + T‐cells, when transferred into tumor‐bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long‐term antitumor function, and appeared to be established as memory T‐cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co‐stimulation in vivo .