Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model

Gaku Matsumoto, Makoto Sunamura, Hiromune Shimamura, Tomohiro Kodama, Wataru Hashimoto, Masao Kobari, Kazunori Kato, Kazuyosi Takeda, Hideo Yagita, Ko Okumura, Hirofumi Hamada, Seiki Matsuno

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)257-264
Number of pages8
JournalSurgery
Volume125
Issue number3
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Surgery

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