Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model
| Autor: | Kazuyosi Takeda, Hideo Yagita, Hiromune Shimamura, Tomohiro Kodama, Seiki Matsuno, Hirofumi Hamada, Wataru Hashimoto, Ko Okumura, Masao Kobari, Makoto Sunamura, Gaku Matsumoto, Kazunori Kato |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_treatment Genetic Vectors Enzyme-Linked Immunosorbent Assay Adenocarcinoma Transfection Interferon-gamma Mice Adjuvants Immunologic In vivo medicine Adjuvant therapy Tumor Cells Cultured Animals Mice Inbred BALB C business.industry Immunotherapy Fibroblasts medicine.disease Interleukin-12 Vaccination Disease Models Animal Cytokine Retroviridae Immunology Colonic Neoplasms Interleukin 12 Surgery Neoplasm Recurrence Local business Adjuvant Spleen |
| Zdroj: | Surgery. 125(3) |
| ISSN: | 0039-6060 |
| Popis: | 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/10 6 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.) |
| Databáze: | OpenAIRE |
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