Allison Martin, M.D.
Medulloblastoma is the most common malignant brain tumor in children. In cases of relapsed or refractory disease there is no known curative therapy. To address this question we have generated fetal mouse brain cells that mimic the most aggressive phenotype of medulloblastoma called “anaplastic” when they are placed into the cerebellum of mature mice. These cells grow tumors that look and behave like aggressive forms of medulloblastoma in humans and contain the gene mutations most commonly found in relapsed disease.
We are using this model of medulloblastoma to test combinations of immune checkpoint inhibitors. Immune checkpoint inhibitors are drugs that unleash the body’s immune system defenses allowing it to seek out and eliminate tumors. Although this therapy does not always work in patients with cancer, when it does the responses are usually very good. Thus far we have found that the administration of 2 different immune checkpoint inhibitors changes the immune cells that infiltrate the brain tumors in a way that makes them more likely to be able to fight the tumors. Although, we have not seen a dramatic benefit in mouse survival overall, a small number of mice benefit from this treatment. This is not dissimilar from clinical trials of these treatments where often only a small percentage of people respond to therapy.
Importantly, we will use this information to test tumors from mice that have and have not responded to this treatment to understand how they are different. We think this will give us information that can be used to help select patients that will benefit most from this type of therapy for medulloblastoma and possibly other pediatric brain tumors in the future. As we continue to understand these effects we want to propose a clinical trial for patients with relapsed and refractory medulloblastoma.
We thank the Childhood Brain Tumor Foundation for your support of this research, it would not be possible without you!
November 2018, Summary