Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model
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- 作者：Gaku Matsumoto ; Makoto Sunamura ; Hiromune Shimamura ; Tomohiro Kodama ; Wataru Hashimoto ; Masao Kobari ; Kazunori Kato ; Kazuyosi Takeda ; Hideo Yagita ; Ko Okumura ; Hirofumi Hamada ; Seiki Matsuno
- 刊名：Surgery
- 出版年：1999
- 出版时间：March 1999
- 年：1999
- 卷：125
- 期：3
- 页码：257-264
- 全文大小：79 K
文摘
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. (Surgery 1999;125:257-64.)