Limitations of the C6/Wistar rat intracerebral glioma model: Implications for evaluating immunotherapy

OBJECTIVE: Intracranial rat glioma models are a useful method for evaluating the efficacy and toxicity of novel therapies for malignant glioma. The C6/Wistar model has been used extensively as a reproducible in vivo model for studying primary brain tumors including anti-glioma immune responses. The objective of the present study is to provide in vivo evidence that the C6 rat glioma model is allogeneic within Wistar rats and is therefore inappropriate for evaluating immune responses. METHODS: Growth patterns and immune responses of C6 cells implanted into the brain and flank of Wistar rats were analyzed and compared to an immunogenic syngeneic model (9L/Fischer). RESULTS: Wistar rats with C6 tumors developed a potent humoral and cellular immune response to the tumor. Wistar rats given simultaneous flank and intracerebral tumors had a survival rate of 100% compared to an 11% survival rate in control animals receiving only intracranial C6 cells. CONCLUSION: The CS rat glioma induces a vigorous immune reaction that may mimic a specific anti-tumor response in Wistar rats. Efficacy of immunotherapy within this model must be cautiously interpreted.