Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system
| Autor: | Yuichi Hata, Tetsuro Kikuchi, Tatsuhiro Joki, Tsuneya Ohno, Tomoaki Miyazaki, Toshiaki Abe, Naoki Kato, Saburo Saitoh, Akihiro Kobayashi |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
CD4-Positive T-Lymphocytes
Interleukin 2 Cancer Research Pathology medicine.medical_specialty Combination therapy Cell Transplantation Genetic Vectors Central nervous system CD8-Positive T-Lymphocytes Recombinant Interleukin Transfection Cancer Vaccines Mice Glioma Tumor Cells Cultured medicine Animals Humans Brain Neoplasms business.industry medicine.disease Interleukin-12 Recombinant Proteins Vaccine therapy Neoplasm Proteins Killer Cells Natural medicine.anatomical_structure Oncology Interleukin 12 Cancer research Interleukin-2 Female business CD8 medicine.drug |
| Zdroj: | International Journal of Cancer. 80:425-430 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/(sici)1097-0215(19990129)80:3<425::aid-ijc15>3.0.co;2-7 |
| Popis: | Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory models. Although IL-12 itself activates strong anti-tumor activity, the combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL-12 has been shown to cure tumor-bearing mice more effectively than either rIL-12 or IL-2-transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL-2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL-2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12 alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL-2 cells and of rIL-12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL-2-producing glioma cells and rIL-12 may be useful in the development of treatment for patients with glioma. |
| Databáze: | OpenAIRE |
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