Open AccessSynergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT
Author(s) -
Masayuki Hisada,
Takayuki Yoshimoto,
Sadahiro Kamiya,
Yasushi Magami,
Hiroko Miyaji,
Toshihiko Yoneto,
Koji Tamada,
Tetsuya Aoki,
Yasuhisa Koyanagi,
Junichiro Mizuguchi
Publication year - 2004
Publication title -
cancer gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.535
H-Index - 86
eISSN - 1476-5500
pISSN - 0929-1903
DOI - 10.1038/sj.cgt.7700676
Subject(s) - cytotoxic t cell , chemokine , ccl21 , cd8 , ctl* , cancer research , in vivo , spleen , immunotherapy , infiltration (hvac) , biology , chemistry , immunology , immune system , in vitro , chemokine receptor , materials science , biochemistry , microbiology and biotechnology , composite material
To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a chemokine CCL21/secondary lymphoid tissue chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo, and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo, and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8(+) T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-gamma production. Neutralization of IFN-gamma or depletion of CD8(+) or CD4(+) T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8(+) T cells, resulting in markedly augmented CTL activity and IFN-gamma production.