TY - JOUR
T1 - Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model
AU - Matsumoto, Gaku
AU - Sunamura, Makoto
AU - Shimamura, Hiromune
AU - Kodama, Tomohiro
AU - Hashimoto, Wataru
AU - Kobari, Masao
AU - Kato, Kazunori
AU - Takeda, Kazuyosi
AU - Yagita, Hideo
AU - Okumura, Ko
AU - Hamada, Hirofumi
AU - Matsuno, Seiki
N1 - Funding Information:
Supported in part by a grant (09557094) from the Ministry of Education, Science, Sports and Culture and a grant from the Society of Digestive Molecular Biology (M.S.).
PY - 1999
Y1 - 1999
N2 - Background. To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. Methods. Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. Results. IL-12/3T3 cells producing 7.2 ng/106 cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. Conclusions. Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers.
AB - Background. To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. Methods. Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. Results. IL-12/3T3 cells producing 7.2 ng/106 cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. Conclusions. Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers.
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U2 - 10.1016/S0039-6060(99)70235-7
DO - 10.1016/S0039-6060(99)70235-7
M3 - Article
C2 - 10076609
AN - SCOPUS:0032952107
VL - 125
SP - 257
EP - 264
JO - Surgery (United States)
JF - Surgery (United States)
SN - 0039-6060
IS - 3
ER -