Interleukin-6 transduction of a rat T9 glioma clone results in attenuated tumorigenicity and induces glioma immunity in Fischer F344 rats

• Published in: Journal of neuro-oncology 1999-01, Vol.45 (3), p.209-218
• Main Authors: GRAF, M. R, MERCHANT, R. E
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - pathology; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Neoplasm - immunology; Antibodies, Neoplasm - pharmacology; Biological and medical sciences; Brain Neoplasms - immunology; Brain Neoplasms - pathology; Carcinogenicity Tests; DNA, Complementary; Female; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Glioblastoma - immunology; Glioblastoma - pathology; Humans; Interleukin-6 - genetics; Interleukin-6 - immunology; Medical sciences; Neoplasm Transplantation; Neurology; Neutralization Tests; Rats; Rats, Inbred F344; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Retroviridae - genetics; Transduction, Genetic; Tumor Cells, Cultured - immunology; Tumor Cells, Cultured - pathology; Tumor Cells, Cultured - transplantation; Tumors of the nervous system. Phacomatoses
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1023/A:1006357424124

We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell line, with a retroviral expression vector containing the human IL-6 cDNA and investigated the effects of IL-6 secretion on glioma formation in the syngeneic Fischer rat. Two subclones producing high and low levels (35 and 3.5 ng/10(6) cells/48 h) of IL-6 were identified and were termed T9.F/IL6/hi and T9.F/IL6/lo, respectively. Subcutaneous (SC) injection of 1 x 10(6) parental T9.F cells resulted in 100% tumor formation and progression. When 1 x 10(6) IL-6 secreting T9.F cells were injected SC, a small palpable tumor formed which sometimes regressed. In this regard, no tumors were detected after 30 days in 76% (13/17) of animals injected with T9.F/IL6/hi cells, whereas only 10% (1/10) of the rats injected with T9.F/IL6/lo cells completely rejected their tumors within this time frame. The addition of an IL-6 neutralizing antibody to the T9.F/IL6/hi SC inoculum followed by an intratumoral injection of the IL-6 neutralizing antibody, seven days later, abrogated the anti-tumor effects. Animals that rejected the IL-6 secreting tumors were 100% protected from subsequent intracranial (IC) challenges with the parental T9.F glioma as well as the original T9 glioblastoma; partially protected from an IC challenge with the unrelated, syngeneic RT-2 glioma; but were not protected from an IC challenge with the syngeneic MadB106 adenocarcinoma. When 1 x 10(4) cells were injected in the brain of naive animals, survival time was significantly increased for those rats implanted with T9.F/IL6/hi cells, but not T9.F/IL6/lo cells, as compared to animals implanted with T9.F parental cells (p = 0.003). This study demonstrates that IL-6 secretion attenuates SC and IC glioma growth and SC rejection of IL-6 secreting T9.F cells induces long-term glioma immunity which is effective in the brain.