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Interleukin-6 Transduction of a Rat T9 Glioma Clone Results in Attenuated Tumorigenicity and Induces Glioma Immunity in Fischer F344 Rats

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Abstract

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/106 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 1×106 parental T9.F cells resulted in 100% tumor formation and progression. When 1×106 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 1×104 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.

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  1. Department of Neurosurgery, Virginia Commonwealth University and Medical College of Virginia, Richmond, Virginia, USA

    Martin R. Graf & Randall E. Merchant

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  1. Martin R. Graf
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Graf, M.R., Merchant, R.E. Interleukin-6 Transduction of a Rat T9 Glioma Clone Results in Attenuated Tumorigenicity and Induces Glioma Immunity in Fischer F344 Rats. J Neurooncol 45, 209–218 (1999). https://doi.org/10.1023/A:1006357424124

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