Medulloblastoma Immunotherapy Overview
VBI has applied its eVLP Platform in the development of a medulloblastoma (“MB”) therapeutic vaccine candidate. With its novel approach, VBI intends to create a MB immunotherapy that will stimulate the patient’s own immune system to identify and attack MB tumor cells, while sparing the vulnerable surrounding brain that is still developing in children.
The Meghan Rose Bradley Foundation, a pediatric brain cancer advocacy organization, provided a grant to fund initial research in ex vivo studies. VBI is evaluating the ability of its MB immunotherapy to stimulate CD4+ and CD8+ T cell responses in peripheral blood mononuclear cells (“PBMCs”) harvested from healthy patients and patients with medulloblastoma; CD4+ and CD8+ immune responses are critical to efficacious anti-tumor immunity. VBI will also monitor several biomarkers predictive of clinical efficacy.
CT scan of a six year old girl showing a MB tumorous mass in the posterior fossa, giving rise to obstructive hydrocephalus.
About Medulloblastoma
VBI-1901 Design
MB Medical Need and Its Relationship to Cytomegalovirus
Medulloblastoma is the most common malignant primary brain tumor in children.1 Standard of care treatment consists of surgical removal of the tumor followed by chemotherapy and radiation, depending on the patient’s staging and age.2 Radiation therapy is rarely administered to children under three years of age because of the high potential for serious neurodevelopmental deficits, further limiting the treatment options available to the youngest patients.3 While modern treatments have led to improvements in survival, the risk of recurrence as well as the long-term side effects associated with surgery, radiation, and chemotherapy underscore the urgent need for new therapeutic approaches.4
Developing a medulloblastoma immunotherapy requires the identification of antigens, used to direct the immune response, that are consistently expressed on tumor cells. Recent research has demonstrated that medulloblastoma tumors are particularly susceptible to infection by cytomegalovirus (“CMV”), with over 90% of some medulloblastoma tumors expressing CMV antigens.5 In addition, antiviral therapies that inhibit CMV replication have been shown to reduce medulloblastoma tumor cell growth, both in vitro and in vivo, suggesting that CMV may increase the malignancy of infected cells.6
Medulloblastoma Resources
- Medulloblastoma information from the American Brain Tumor Association. Visit resource >>
- Brain cancer resources for patients from the National Cancer Institute. Visit resource >>
- Medulloblastoma overview from the Mayo Clinic. Visit resource >>
- Detection of CMV in tumors of patients diagnosed with medulloblastoma. Visit resource >>
References
- Gopalakrishnan V, Tao RH, Dobson T, Brugmann W, Khatua S. Medulloblastoma development: tumor biology informs treatment decisions. CNS Oncol. 2015;4(2):79-89.
- Von hoff K, Rutkowski S. Medulloblastoma. Curr Treat Options Neurol. 2012;14(4):416-26.
- Askins MA, Moore BD. Preventing neurocognitive late effects in childhood cancer survivors. J Child Neurol. 2008;23(10):1160-71.
- Mulhern RK, Merchant TE, Gajjar A, Reddick WE, Kun LE. Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol. 2004;5(7):399-408.
- Baryawno N, Rahbar A, Wolmer-solberg N, et al. Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J Clin Invest. 2011;121(10):4043-55.
- Baryawno N, Rahbar A, Wolmer-solberg N, et al. Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J Clin Invest. 2011;121(10):4043-55.
- Arellano M, Lonial S. Clinical uses of GM-CSF, a critical appraisal and update. Biologics. 2008;2(1):13-27.