Immunotherapy Shown Effective in Brain Tumor Animal Test

Burkhard Becher (University of Zurich)

Researchers at University of Zurich in Switzerland tested a therapy in lab mice that harnesses the immune system to fight glioblastoma, an aggressive form of brain cancer. The team led by Zurich immunologist Burkhard Becher reported its findings yesterday online in the Journal of Experimental Medicine (paid subscription required) and seeks commercial partners for accelerated clinical trials.

Becher and colleagues tested an immunotherapy strategy to treat advanced cancers, particularly brain tumors where T-cells accumulate in the brain to hinder rather than help the immune system fight the tumor. In this case, the cancer was glioblastoma, an aggressive, complex, and highly malignant type of brain cancer.

The researchers first tested the immune signaling protein Interleukin-12 in lab mice with glioblastoma. The team produced Interleukin-12 inside the tumor, which in its early stages stimulated an immune response that attacked and rejected the tumor.

In the next stage of the study, the team waited until the tumor was large and the life expectancy of the test animals was reduced to a few weeks. Under these conditions, Interleukin-12 did provoke an immune response in the mice, but the tumor rejection rate dropped to only about a quarter of the cases.

In the third stage of the study, the Zurich researchers combined Interleukin-12 inside the tumor with a drug that blocks receptors of the cytotoxic T-lymphocyte-associated or CTLA-4 gene that sends inhibitory signals to T cells. The combination of Interleukin-12 and CTLA-4 blockers succeeded in raising the tumor rejection rate to 80 percent, which the researchers say they successfully tested again in a tumor model more like those in brain cancer patients.

The Zurich team is seeking commercial partners to quickly test this therapy strategy in clinical trials. “I have rarely seen such convincing data in preclinical glioma treatment”, says co-author and neuro-oncologist Michael Weller in a university statement. “That’s why this development should be tested as soon as possible in clinical trials.”

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